High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases
- Jia, Xiaoxiao, Crawford, Jeremy, Gebregzabher, Deborah, Monson, Ebony, Mettelman, Robert, Wan, Yanmin, Ren, Yanqin, Chou, Janet, Novak, Tanya, McQuilten, Hayley, Clarke, Michele, Bachem, Annabell, Foo, Isabelle, Fritzlar, Svenja, Carrera Montoya, Julio, Trenerry, Alice, Nie, Shuai, Leeming, Michael, Nguyen, Thi, Kedzierski, Lukasz, Littler, Dene, Kueh, Andrew, Cardamone, Tina, Wong, Chinn, Hensen, Luca, Cabug, Aira, Laguna, Jaime, Agrawal, Mona, Flerlage, Tim, Berzins, Stuart
- Authors: Jia, Xiaoxiao , Crawford, Jeremy , Gebregzabher, Deborah , Monson, Ebony , Mettelman, Robert , Wan, Yanmin , Ren, Yanqin , Chou, Janet , Novak, Tanya , McQuilten, Hayley , Clarke, Michele , Bachem, Annabell , Foo, Isabelle , Fritzlar, Svenja , Carrera Montoya, Julio , Trenerry, Alice , Nie, Shuai , Leeming, Michael , Nguyen, Thi , Kedzierski, Lukasz , Littler, Dene , Kueh, Andrew , Cardamone, Tina , Wong, Chinn , Hensen, Luca , Cabug, Aira , Laguna, Jaime , Agrawal, Mona , Flerlage, Tim , Berzins, Stuart
- Date: 2024
- Type: Text , Journal article
- Relation: Cell Vol. 187, no. 17 (2024), p. 4586-4604.e20
- Full Text:
- Reviewed:
- Description: Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah
- Authors: Jia, Xiaoxiao , Crawford, Jeremy , Gebregzabher, Deborah , Monson, Ebony , Mettelman, Robert , Wan, Yanmin , Ren, Yanqin , Chou, Janet , Novak, Tanya , McQuilten, Hayley , Clarke, Michele , Bachem, Annabell , Foo, Isabelle , Fritzlar, Svenja , Carrera Montoya, Julio , Trenerry, Alice , Nie, Shuai , Leeming, Michael , Nguyen, Thi , Kedzierski, Lukasz , Littler, Dene , Kueh, Andrew , Cardamone, Tina , Wong, Chinn , Hensen, Luca , Cabug, Aira , Laguna, Jaime , Agrawal, Mona , Flerlage, Tim , Berzins, Stuart
- Date: 2024
- Type: Text , Journal article
- Relation: Cell Vol. 187, no. 17 (2024), p. 4586-4604.e20
- Full Text:
- Reviewed:
- Description: Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah
Methodological optimisation of thymocyte isolation and cryopreservation of human thymus samples
- Hagen, Ruth, Xu, Calvin, Koay, Hui-Fern, Konstantinov, Igor, Berzins, Stuart, Kedzierska, Katherine, van de Sandt, Carolien
- Authors: Hagen, Ruth , Xu, Calvin , Koay, Hui-Fern , Konstantinov, Igor , Berzins, Stuart , Kedzierska, Katherine , van de Sandt, Carolien
- Date: 2024
- Type: Text , Journal article
- Relation: Journal of Immunological Methods Vol. 528, no. (2024), p.
- Full Text:
- Reviewed:
- Description: Premature lymphocytes develop into non-autoreactive, mature naïve CD4+ or CD8+ T cells in the thymus before entering the circulation. However, in-depth characterization of human thymocyte development remains challenging due to limited availability of human thymus samples and the fragile nature of thymocyte populations. Thymocytes often do not survive cryopreservation and thawing procedures, especially the fragile CD4+CD8+ double positive population. It is generally recommended to use fresh human thymus tissue on the day of excision to avoid any biases in thymocyte composition. This hampers the possibility to perform multiple experiments on the same thymus sample. To establish how the thymocyte viability and composition can be maintained, we compared two thymocyte isolation methods used for human and/or mice thymi, three cryopreservation methods in combination with our most gentle thawing technique. Based on our findings we established that fresh human thymi remain viable in cold storage for up to two days post-surgery without compromising thymocyte composition. Thymocytes can be cryopreserved if required, although the CD4+CD8+ double positive populations may be reduced. Our study provides thoroughly optimized methods to study human thymocyte development over a considerable time-frame post-surgery. © 2024 The Authors
- Authors: Hagen, Ruth , Xu, Calvin , Koay, Hui-Fern , Konstantinov, Igor , Berzins, Stuart , Kedzierska, Katherine , van de Sandt, Carolien
- Date: 2024
- Type: Text , Journal article
- Relation: Journal of Immunological Methods Vol. 528, no. (2024), p.
- Full Text:
- Reviewed:
- Description: Premature lymphocytes develop into non-autoreactive, mature naïve CD4+ or CD8+ T cells in the thymus before entering the circulation. However, in-depth characterization of human thymocyte development remains challenging due to limited availability of human thymus samples and the fragile nature of thymocyte populations. Thymocytes often do not survive cryopreservation and thawing procedures, especially the fragile CD4+CD8+ double positive population. It is generally recommended to use fresh human thymus tissue on the day of excision to avoid any biases in thymocyte composition. This hampers the possibility to perform multiple experiments on the same thymus sample. To establish how the thymocyte viability and composition can be maintained, we compared two thymocyte isolation methods used for human and/or mice thymi, three cryopreservation methods in combination with our most gentle thawing technique. Based on our findings we established that fresh human thymi remain viable in cold storage for up to two days post-surgery without compromising thymocyte composition. Thymocytes can be cryopreserved if required, although the CD4+CD8+ double positive populations may be reduced. Our study provides thoroughly optimized methods to study human thymocyte development over a considerable time-frame post-surgery. © 2024 The Authors
Thymic development of human natural killer T cells : recent advances and implications for immunotherapy
- Pellicci, Daniel, Tavakolinia, Naeimeh, Perriman, Louis, Berzins, Stuart, Menne, Christopher
- Authors: Pellicci, Daniel , Tavakolinia, Naeimeh , Perriman, Louis , Berzins, Stuart , Menne, Christopher
- Date: 2024
- Type: Text , Journal article , Review
- Relation: Frontiers in Immunology Vol. 15, no. (2024), p.
- Full Text:
- Reviewed:
- Description: Invariant natural killer T (iNKT) cells are a subset of lipid-reactive, unconventional T cells that have anti-tumor properties that make them a promising target for cancer immunotherapy. Recent studies have deciphered the developmental pathway of human MAIT and V
- Authors: Pellicci, Daniel , Tavakolinia, Naeimeh , Perriman, Louis , Berzins, Stuart , Menne, Christopher
- Date: 2024
- Type: Text , Journal article , Review
- Relation: Frontiers in Immunology Vol. 15, no. (2024), p.
- Full Text:
- Reviewed:
- Description: Invariant natural killer T (iNKT) cells are a subset of lipid-reactive, unconventional T cells that have anti-tumor properties that make them a promising target for cancer immunotherapy. Recent studies have deciphered the developmental pathway of human MAIT and V
A three-stage developmental pathway for human Vγ9Vδ2 T cells within the postnatal thymus
- Perriman, Louis, Tavakolinia, Naeimeh, Jalali, Sedigheh, Li, Shuo, Hickey, Peter, Amann-Zalcenstein, Daniela, Ho, William, Baldwin, Tracey, Piers, Adam, Konstantinov, Igor, Anderson, Jeremy, Stanley, Edouard, Licciardi, Paul, Kannourakis, George, Naik, Shalin, Koay, Hui-Fern, Mackay, Laura, Berzins, Stuart, Pellicci, Daniel
- Authors: Perriman, Louis , Tavakolinia, Naeimeh , Jalali, Sedigheh , Li, Shuo , Hickey, Peter , Amann-Zalcenstein, Daniela , Ho, William , Baldwin, Tracey , Piers, Adam , Konstantinov, Igor , Anderson, Jeremy , Stanley, Edouard , Licciardi, Paul , Kannourakis, George , Naik, Shalin , Koay, Hui-Fern , Mackay, Laura , Berzins, Stuart , Pellicci, Daniel
- Date: 2023
- Type: Text , Journal article
- Relation: Science Immunology Vol. 8, no. 85 (2023), p.
- Full Text: false
- Reviewed:
- Description: V
Distinct subpopulations of DN1 thymocytes exhibit preferential gamma delta T lineage potential
- Oh, Seungyoul, Liu, Xin, Tomei, Sara, Luo, Mengxiao, Skinner, Jarrod, Berzins, Stuart, Naik, Shalin, Gray, Daniel, Chong, Mark
- Authors: Oh, Seungyoul , Liu, Xin , Tomei, Sara , Luo, Mengxiao , Skinner, Jarrod , Berzins, Stuart , Naik, Shalin , Gray, Daniel , Chong, Mark
- Date: 2023
- Type: Text , Journal article
- Relation: Frontiers in Immunology Vol. 14, no. (2023), p.
- Full Text:
- Reviewed:
- Description: The
- Authors: Oh, Seungyoul , Liu, Xin , Tomei, Sara , Luo, Mengxiao , Skinner, Jarrod , Berzins, Stuart , Naik, Shalin , Gray, Daniel , Chong, Mark
- Date: 2023
- Type: Text , Journal article
- Relation: Frontiers in Immunology Vol. 14, no. (2023), p.
- Full Text:
- Reviewed:
- Description: The
Divergent molecular networks program functionally distinct CD8+skin-resident memory T cells
- Park, Simone, Christo, Susan, Wells, Alexandria, Gandolfo, Luke, Zaid, Ali, Alexandre, Yannick, Burn, Thomas, Schröder, Jan, Collins, Nicholas, Han, Seong-Ji, Guillaume, Stephane, Evrard, Maximilien, Castellucci, Clara, Davies, Brooke, Osman, Maleika, Obers, Andreas, McDonald, Keely, Wang, Huimeng, Mueller, Scott, Kannourakis, George, Berzins, Stuart, Mielke, Lisa, Carbone, Francis, Kallies, Axel, Speed, Terence, Belkaid, Yasmine, MacKay, Laura
- Authors: Park, Simone , Christo, Susan , Wells, Alexandria , Gandolfo, Luke , Zaid, Ali , Alexandre, Yannick , Burn, Thomas , Schröder, Jan , Collins, Nicholas , Han, Seong-Ji , Guillaume, Stephane , Evrard, Maximilien , Castellucci, Clara , Davies, Brooke , Osman, Maleika , Obers, Andreas , McDonald, Keely , Wang, Huimeng , Mueller, Scott , Kannourakis, George , Berzins, Stuart , Mielke, Lisa , Carbone, Francis , Kallies, Axel , Speed, Terence , Belkaid, Yasmine , MacKay, Laura
- Date: 2023
- Type: Text , Journal article
- Relation: Science Vol. 382, no. 6674 (2023), p. 1073-1079
- Full Text: false
- Reviewed:
- Description: Skin-resident CD8+T cells include distinct interferon-g-producing [tissue-resident memory T type 1 (TRM1)] and interleukin-17 (IL-17)-producing (TRM17) subsets that differentially contribute to immune responses. However, whether these populations use common mechanisms to establish tissue residence is unknown. In this work, we show that TRM1 and TRM17 cells navigate divergent trajectories to acquire tissue residency in the skin. TRM1 cells depend on a T-bet-Hobit-IL-15 axis, whereas TRM17 cells develop independently of these factors. Instead, c-Maf commands a tissue-resident program in TRM17 cells parallel to that induced by Hobit in TRM1 cells, with an ICOS-c-Maf-IL-7 axis pivotal to TRM17 cell commitment. Accordingly, by targeting this pathway, skin TRM17 cells can be ablated without compromising their TRM1 counterparts. Thus, skin-resident T cells rely on distinct molecular circuitries, which can be exploited to strategically modulate local immunity. © 2023 American Association for the Advancement of Science. All rights reserved.
Effect of hydralazine on angiotensin II-induced abdominal aortic aneurysm in apolipoprotein e-deficient mice
- Wang, Yutang, Sargisson, Owen, Nguyen, Dinh, Parker, Ketura, Pyke, Stephan, Alramahi, Ahmed, Thihlum, Liam, Fang, Yan, Wallace, Morgan, Berzins, Stuart, Oqueli, Ernesto, Magliano, Dianna, Golledge, Jonathan
- Authors: Wang, Yutang , Sargisson, Owen , Nguyen, Dinh , Parker, Ketura , Pyke, Stephan , Alramahi, Ahmed , Thihlum, Liam , Fang, Yan , Wallace, Morgan , Berzins, Stuart , Oqueli, Ernesto , Magliano, Dianna , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: International Journal of Molecular Sciences Vol. 24, no. 21 (2023), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The rupture of an abdominal aortic aneurysm (AAA) causes about 200,000 deaths worldwide each year. However, there are currently no effective drug therapies to prevent AAA formation or, when present, to decrease progression and rupture, highlighting an urgent need for more research in this field. Increased vascular inflammation and enhanced apoptosis of vascular smooth muscle cells (VSMCs) are implicated in AAA formation. Here, we investigated whether hydralazine, which has anti-inflammatory and anti-apoptotic properties, inhibited AAA formation and pathological hallmarks. In cultured VSMCs, hydralazine (100
- Authors: Wang, Yutang , Sargisson, Owen , Nguyen, Dinh , Parker, Ketura , Pyke, Stephan , Alramahi, Ahmed , Thihlum, Liam , Fang, Yan , Wallace, Morgan , Berzins, Stuart , Oqueli, Ernesto , Magliano, Dianna , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: International Journal of Molecular Sciences Vol. 24, no. 21 (2023), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The rupture of an abdominal aortic aneurysm (AAA) causes about 200,000 deaths worldwide each year. However, there are currently no effective drug therapies to prevent AAA formation or, when present, to decrease progression and rupture, highlighting an urgent need for more research in this field. Increased vascular inflammation and enhanced apoptosis of vascular smooth muscle cells (VSMCs) are implicated in AAA formation. Here, we investigated whether hydralazine, which has anti-inflammatory and anti-apoptotic properties, inhibited AAA formation and pathological hallmarks. In cultured VSMCs, hydralazine (100
A high-dimensional cytometry atlas of peripheral blood over the human life span
- Jalali, Sedigheh, Harpur, Christopher, Piers, Adam, Auladell, Maria, Perriman, Louis, Li, Shuo, An, Kim, Anderson, Jeremy, Berzins, Stuart, Licciardi, Paul, Ashhurst, Thomas, Konstantinov, Igor, Pellicci, Daniel
- Authors: Jalali, Sedigheh , Harpur, Christopher , Piers, Adam , Auladell, Maria , Perriman, Louis , Li, Shuo , An, Kim , Anderson, Jeremy , Berzins, Stuart , Licciardi, Paul , Ashhurst, Thomas , Konstantinov, Igor , Pellicci, Daniel
- Date: 2022
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 100, no. 10 (2022), p. 805-821
- Full Text:
- Reviewed:
- Description: Age can profoundly affect susceptibility to a broad range of human diseases. Children are more susceptible to some infectious diseases such as diphtheria and pertussis, while in others, such as coronavirus disease 2019 and hepatitis A, they are more protected compared with adults. One explanation is that the composition of the immune system is a major contributing factor to disease susceptibility and severity. While most studies of the human immune system have focused on adults, how the immune system changes after birth remains poorly understood. Here, using high-dimensional spectral flow cytometry and computational methods for data integration, we analyzed more than 50 populations of immune cells in the peripheral blood, generating an immune cell atlas that defines the healthy human immune system from birth up to 75 years of age. We focused our efforts on children under 18 years old, revealing major changes in immune cell populations after birth and in children of schooling age. Specifically, CD4+ T effector memory cells, V
- Authors: Jalali, Sedigheh , Harpur, Christopher , Piers, Adam , Auladell, Maria , Perriman, Louis , Li, Shuo , An, Kim , Anderson, Jeremy , Berzins, Stuart , Licciardi, Paul , Ashhurst, Thomas , Konstantinov, Igor , Pellicci, Daniel
- Date: 2022
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 100, no. 10 (2022), p. 805-821
- Full Text:
- Reviewed:
- Description: Age can profoundly affect susceptibility to a broad range of human diseases. Children are more susceptible to some infectious diseases such as diphtheria and pertussis, while in others, such as coronavirus disease 2019 and hepatitis A, they are more protected compared with adults. One explanation is that the composition of the immune system is a major contributing factor to disease susceptibility and severity. While most studies of the human immune system have focused on adults, how the immune system changes after birth remains poorly understood. Here, using high-dimensional spectral flow cytometry and computational methods for data integration, we analyzed more than 50 populations of immune cells in the peripheral blood, generating an immune cell atlas that defines the healthy human immune system from birth up to 75 years of age. We focused our efforts on children under 18 years old, revealing major changes in immune cell populations after birth and in children of schooling age. Specifically, CD4+ T effector memory cells, V
Plasma signaling factors in patients with langerhans cell histiocytosis (LCH) correlate with relative frequencies of LCH cells and t cells within lesions
- Mitchell, Jenée, Kvedaraite, Egle, von Bahr Greenwood, Tatiana, Lourda, Magda, Henter, Jan-Inge, Berzins, Stuart, Kannourakis, George
- Authors: Mitchell, Jenée , Kvedaraite, Egle , von Bahr Greenwood, Tatiana , Lourda, Magda , Henter, Jan-Inge , Berzins, Stuart , Kannourakis, George
- Date: 2022
- Type: Text , Journal article
- Relation: Frontiers in Pediatrics Vol. 10, no. (2022), p.
- Full Text:
- Reviewed:
- Description: Langerhans cell histiocytosis (LCH) lesions contain an inflammatory infiltrate of immune cells including myeloid-derived LCH cells. Cell-signaling proteins within the lesion environment suggest that LCH cells and T cells contribute majorly to the inflammation. Foxp3+ regulatory T cells (Tregs) are enriched in lesions and blood from patients with LCH and are likely involved in LCH pathogenesis. In contrast, mucosal associated invariant T (MAIT) cells are reduced in blood from these patients and the consequence of this is unknown. Serum/plasma levels of cytokines have been associated with LCH disease extent and may play a role in the recruitment of cells to lesions. We investigated whether plasma signaling factors differed between patients with active and non-active LCH. Cell-signaling factors (38 analytes total) were measured in patient plasma and cell populations from matched lesions and/or peripheral blood were enumerated. This study aimed at understanding whether plasma factors corresponded with LCH cells and/or LCH-associated T cell subsets in patients with LCH. We identified several associations between plasma factors and lesional/circulating immune cell populations, thus highlighting new factors as potentially important in LCH pathogenesis. This study highlights plasma cell-signaling factors that are associated with LCH cells, MAIT cells or Tregs in patients, thus they are potentially important in LCH pathogenesis. Further study into these associations is needed to determine whether these factors may become suitable prognostic indicators or therapeutic targets to benefit patients. Copyright © 2022 Mitchell, Kvedaraite, von Bahr Greenwood, Lourda, Henter, Berzins and Kannourakis.
- Authors: Mitchell, Jenée , Kvedaraite, Egle , von Bahr Greenwood, Tatiana , Lourda, Magda , Henter, Jan-Inge , Berzins, Stuart , Kannourakis, George
- Date: 2022
- Type: Text , Journal article
- Relation: Frontiers in Pediatrics Vol. 10, no. (2022), p.
- Full Text:
- Reviewed:
- Description: Langerhans cell histiocytosis (LCH) lesions contain an inflammatory infiltrate of immune cells including myeloid-derived LCH cells. Cell-signaling proteins within the lesion environment suggest that LCH cells and T cells contribute majorly to the inflammation. Foxp3+ regulatory T cells (Tregs) are enriched in lesions and blood from patients with LCH and are likely involved in LCH pathogenesis. In contrast, mucosal associated invariant T (MAIT) cells are reduced in blood from these patients and the consequence of this is unknown. Serum/plasma levels of cytokines have been associated with LCH disease extent and may play a role in the recruitment of cells to lesions. We investigated whether plasma signaling factors differed between patients with active and non-active LCH. Cell-signaling factors (38 analytes total) were measured in patient plasma and cell populations from matched lesions and/or peripheral blood were enumerated. This study aimed at understanding whether plasma factors corresponded with LCH cells and/or LCH-associated T cell subsets in patients with LCH. We identified several associations between plasma factors and lesional/circulating immune cell populations, thus highlighting new factors as potentially important in LCH pathogenesis. This study highlights plasma cell-signaling factors that are associated with LCH cells, MAIT cells or Tregs in patients, thus they are potentially important in LCH pathogenesis. Further study into these associations is needed to determine whether these factors may become suitable prognostic indicators or therapeutic targets to benefit patients. Copyright © 2022 Mitchell, Kvedaraite, von Bahr Greenwood, Lourda, Henter, Berzins and Kannourakis.
Modulation of TCR signalling components occurs prior to positive selection and lineage commitment in iNKT cells
- Dinh, Xuyen, Stanley, Dragana, Smith, Letitia, Moreau, Morgane, Berzins, Stuart
- Authors: Dinh, Xuyen , Stanley, Dragana , Smith, Letitia , Moreau, Morgane , Berzins, Stuart
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: iNKT cells play a critical role in controlling the strength and character of adaptive and innate immune responses. Their unique functional characteristics are induced by a transcriptional program initiated by positive selection mediated by CD1d expressed by CD4+CD8+ (double positive, DP) thymocytes. Here, using a novel Vα14 TCR transgenic strain bearing greatly expanded numbers of CD24hiCD44loNKT cells, we examined transcriptional events in four immature thymic iNKT cell subsets. A transcriptional regulatory network approach identified transcriptional changes in proximal components of the TCR signalling cascade in DP NKT cells. Subsequently, positive and negative selection, and lineage commitment, occurred at the transition from DP NKT to CD4 NKT. Thus, this study introduces previously unrecognised steps in early NKT cell development, and separates the events associated with modulation of the T cell signalling cascade prior to changes associated with positive selection and lineage commitment. © 2021, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Stuart Berzins” is provided in this record**
- Authors: Dinh, Xuyen , Stanley, Dragana , Smith, Letitia , Moreau, Morgane , Berzins, Stuart
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: iNKT cells play a critical role in controlling the strength and character of adaptive and innate immune responses. Their unique functional characteristics are induced by a transcriptional program initiated by positive selection mediated by CD1d expressed by CD4+CD8+ (double positive, DP) thymocytes. Here, using a novel Vα14 TCR transgenic strain bearing greatly expanded numbers of CD24hiCD44loNKT cells, we examined transcriptional events in four immature thymic iNKT cell subsets. A transcriptional regulatory network approach identified transcriptional changes in proximal components of the TCR signalling cascade in DP NKT cells. Subsequently, positive and negative selection, and lineage commitment, occurred at the transition from DP NKT to CD4 NKT. Thus, this study introduces previously unrecognised steps in early NKT cell development, and separates the events associated with modulation of the T cell signalling cascade prior to changes associated with positive selection and lineage commitment. © 2021, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Stuart Berzins” is provided in this record**
Sphingosine 1-phosphate receptor 5 (S1PR5) regulates the peripheral retention of tissue-resident lymphocytes
- Evrard, Maximilien, Wynne-Jones, Erica, Peng, Changwei, Kannourakis, George, Berzins, Stuart
- Authors: Evrard, Maximilien , Wynne-Jones, Erica , Peng, Changwei , Kannourakis, George , Berzins, Stuart
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Experimental Medicine Vol. 219, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: Tissue-resident memory T (TRM) cells provide long-lasting immune protection. One of the key events controlling TRM cell development is the local retention of TRM cell precursors coupled to downregulation of molecules necessary for tissue exit. Sphingosine-1-phosphate receptor 5 (S1PR5) is a migratory receptor with an uncharted function in T cells. Here, we show that S1PR5 plays a critical role in T cell infiltration and emigration from peripheral organs, as well as being specifically downregulated in TRM cells. Consequentially, TRM cell development was selectively impaired upon ectopic expression of S1pr5, whereas loss of S1pr5 enhanced skin TRM cell formation by promoting peripheral T cell sequestration. Importantly, we found that T-bet and ZEB2 were required for S1pr5 induction and that local TGF-β signaling was necessary to promote coordinated Tbx21, Zeb2, and S1pr5 downregulation. Moreover, S1PR5-mediated control of tissue residency was conserved across innate and adaptive immune compartments. Together, these results identify the T-bet-ZEB2-S1PR5 axis as a previously unappreciated mechanism modulating the generation of tissue-resident lymphocytes. © 2021 Evrard et al.
- Authors: Evrard, Maximilien , Wynne-Jones, Erica , Peng, Changwei , Kannourakis, George , Berzins, Stuart
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Experimental Medicine Vol. 219, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: Tissue-resident memory T (TRM) cells provide long-lasting immune protection. One of the key events controlling TRM cell development is the local retention of TRM cell precursors coupled to downregulation of molecules necessary for tissue exit. Sphingosine-1-phosphate receptor 5 (S1PR5) is a migratory receptor with an uncharted function in T cells. Here, we show that S1PR5 plays a critical role in T cell infiltration and emigration from peripheral organs, as well as being specifically downregulated in TRM cells. Consequentially, TRM cell development was selectively impaired upon ectopic expression of S1pr5, whereas loss of S1pr5 enhanced skin TRM cell formation by promoting peripheral T cell sequestration. Importantly, we found that T-bet and ZEB2 were required for S1pr5 induction and that local TGF-β signaling was necessary to promote coordinated Tbx21, Zeb2, and S1pr5 downregulation. Moreover, S1PR5-mediated control of tissue residency was conserved across innate and adaptive immune compartments. Together, these results identify the T-bet-ZEB2-S1PR5 axis as a previously unappreciated mechanism modulating the generation of tissue-resident lymphocytes. © 2021 Evrard et al.
The attributes of plakins in cancer and disease: perspectives on ovarian cancer progression, chemoresistance and recurrence
- Wesley, Tamsin, Berzins, Stuart, Kannourakis, George, Ahmed, Nuzhat
- Authors: Wesley, Tamsin , Berzins, Stuart , Kannourakis, George , Ahmed, Nuzhat
- Date: 2021
- Type: Text , Journal article , Review
- Relation: Cell Communication and Signaling Vol. 19, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: The plakin family of cytoskeletal proteins play an important role in cancer progression yet are under-studied in cancer, especially ovarian cancer. These large cytoskeletal proteins have primary roles in the maintenance of cytoskeletal integrity but are also associated with scaffolds of intermediate filaments and hemidesmosomal adhesion complexes mediating signalling pathways that regulate cellular growth, migration, invasion and differentiation as well as stress response. Abnormalities of plakins, and the closely related spectraplakins, result in diseases of the skin, striated muscle and nervous tissue. Their prevalence in epithelial cells suggests that plakins may play a role in epithelial ovarian cancer progression and recurrence. In this review article, we explore the roles of plakins, particularly plectin, periplakin and envoplakin in disease-states and cancers with emphasis on ovarian cancer. We discuss the potential role the plakin family of proteins play in regulating cancer cell growth, survival, migration, invasion and drug resistance. We highlight potential relationships between plakins, epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) and discuss how interaction of these processes may affect ovarian cancer progression, chemoresistance and ultimately recurrence. We propose that molecular changes in the expression of plakins leads to the transition of benign ovarian tumours to carcinomas, as well as floating cellular aggregates (commonly known as spheroids) in the ascites microenvironment, which may contribute to the sustenance and progression of the disease. In this review, attempts have been made to understand the crucial changes in plakin expression in relation to progression and recurrence of ovarian cancer. [MediaObject not available: see fulltext.] © 2021, The Author(s).
- Authors: Wesley, Tamsin , Berzins, Stuart , Kannourakis, George , Ahmed, Nuzhat
- Date: 2021
- Type: Text , Journal article , Review
- Relation: Cell Communication and Signaling Vol. 19, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: The plakin family of cytoskeletal proteins play an important role in cancer progression yet are under-studied in cancer, especially ovarian cancer. These large cytoskeletal proteins have primary roles in the maintenance of cytoskeletal integrity but are also associated with scaffolds of intermediate filaments and hemidesmosomal adhesion complexes mediating signalling pathways that regulate cellular growth, migration, invasion and differentiation as well as stress response. Abnormalities of plakins, and the closely related spectraplakins, result in diseases of the skin, striated muscle and nervous tissue. Their prevalence in epithelial cells suggests that plakins may play a role in epithelial ovarian cancer progression and recurrence. In this review article, we explore the roles of plakins, particularly plectin, periplakin and envoplakin in disease-states and cancers with emphasis on ovarian cancer. We discuss the potential role the plakin family of proteins play in regulating cancer cell growth, survival, migration, invasion and drug resistance. We highlight potential relationships between plakins, epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) and discuss how interaction of these processes may affect ovarian cancer progression, chemoresistance and ultimately recurrence. We propose that molecular changes in the expression of plakins leads to the transition of benign ovarian tumours to carcinomas, as well as floating cellular aggregates (commonly known as spheroids) in the ascites microenvironment, which may contribute to the sustenance and progression of the disease. In this review, attempts have been made to understand the crucial changes in plakin expression in relation to progression and recurrence of ovarian cancer. [MediaObject not available: see fulltext.] © 2021, The Author(s).
A role for MAIT cells in colorectal cancer
- Berzins, Stuart, Wallace, Morgan, Kannourakis, George, Kelly, Jason
- Authors: Berzins, Stuart , Wallace, Morgan , Kannourakis, George , Kelly, Jason
- Date: 2020
- Type: Text , Journal article , Review
- Relation: Frontiers in Immunology Vol. 11, no. (2020), p.
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- Description: MAIT cells are MR1-restricted T cells that are well-known for their anti-microbial properties, but they have recently been associated with different forms of cancer. Several studies have reported activated MAIT cells within the microenvironment of colorectal tumors, but there is conjecture about the nature of their response and whether they are contributing to anti-tumor immunity, or to the progression of the disease. We have reviewed the current state of knowledge about the role of MAIT cells in colorectal cancer, including their likely influence when activated and potential sources of stimulation in the tumor microenvironment. The prospects for MAIT cells being used in clinical settings as biomarkers or as targets of new immunotherapies designed to harness their function are discussed. © Copyright © 2020 Berzins, Wallace, Kannourakis and Kelly.
- Authors: Berzins, Stuart , Wallace, Morgan , Kannourakis, George , Kelly, Jason
- Date: 2020
- Type: Text , Journal article , Review
- Relation: Frontiers in Immunology Vol. 11, no. (2020), p.
- Full Text:
- Reviewed:
- Description: MAIT cells are MR1-restricted T cells that are well-known for their anti-microbial properties, but they have recently been associated with different forms of cancer. Several studies have reported activated MAIT cells within the microenvironment of colorectal tumors, but there is conjecture about the nature of their response and whether they are contributing to anti-tumor immunity, or to the progression of the disease. We have reviewed the current state of knowledge about the role of MAIT cells in colorectal cancer, including their likely influence when activated and potential sources of stimulation in the tumor microenvironment. The prospects for MAIT cells being used in clinical settings as biomarkers or as targets of new immunotherapies designed to harness their function are discussed. © Copyright © 2020 Berzins, Wallace, Kannourakis and Kelly.
- Mitchell, Jenée, Kelly, Jason, Kvedaraite, E., von Bahr Greenwood, Tatiana, Henter, Jan-Inge, Pellicci, Daniel, Berzins, Stuart, Kannourakis, George
- Authors: Mitchell, Jenée , Kelly, Jason , Kvedaraite, E. , von Bahr Greenwood, Tatiana , Henter, Jan-Inge , Pellicci, Daniel , Berzins, Stuart , Kannourakis, George
- Date: 2020
- Type: Text , Journal article
- Relation: Clinical Immunology Vol. 215, no. (2020), p.
- Full Text: false
- Reviewed:
- Description: Langerhans cell histiocytosis (LCH) lesions contain myeloid lineage ‘LCH’ cells. Regulatory T cells (Tregs) are also enriched within lesions, although their role in LCH pathogenesis is unknown. LCH cells are thought to produce the transforming growth factor beta (TGF-β) within lesions, however whether Tregs contribute is unestablished. Using flow cytometry, we analyzed relative frequencies of live Tregs from LCH patients and identified CD56 expression and TGF-β production by lesion Tregs. While CD56+ Tregs were enriched in lesions, overall CD56+ T cells were reduced in the blood from active LCH patients compared to non-active disease patients, and there was a negative correlation between CD8+CD56+ T cells and Tregs. We propose that inducing a Treg phenotype in T cells such as CD56+ T cells may be a mechanism by which LCH cells divert inflammatory T cell responses. Thus, Tregs within LCH lesions are likely an important component in LCH pathogenesis. © 2020
High CD26 and low CD94 expression identifies an IL-23 responsive Vδ2+ T Cell subset with a MAIT cell-like transcriptional profile
- Wragg, Kathleen, Tan, Hyon, Kristensen, Anne, Nguyen-Robertson, Catriona, Kelleher, Anthony, Parsons, Matthew, Wheatley, Adam, Berzins, Stuart, Pellicci, Daniel, Kent, Stephen, Juno, Jennifer
- Authors: Wragg, Kathleen , Tan, Hyon , Kristensen, Anne , Nguyen-Robertson, Catriona , Kelleher, Anthony , Parsons, Matthew , Wheatley, Adam , Berzins, Stuart , Pellicci, Daniel , Kent, Stephen , Juno, Jennifer
- Date: 2020
- Type: Text , Journal article
- Relation: Cell Reports Vol. 31, no. 11 (2020), p.
- Full Text:
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- Description: Vδ2+ T cells play a critical role in immunity to micro-organisms and cancer but exhibit substantial heterogeneity in humans. Here, we demonstrate that CD26 and CD94 define transcriptionally, phenotypically, and functionally distinct Vδ2+ T cell subsets. Despite distinct antigen specificities, CD26hiCD94lo Vδ2+ cells exhibit substantial similarities to CD26hi mucosal-associated invariant T (MAIT) cells, although CD26− Vδ2+ cells exhibit cytotoxic, effector-like profiles. At birth, the Vδ2+Vγ9+ population is dominated by CD26hiCD94lo cells; during adolescence and adulthood, Vδ2+ cells acquire CD94/NKG2A expression and the relative frequency of the CD26hiCD94lo subset declines. Critically, exposure of the CD26hiCD94lo subset to phosphoantigen in the context of interleukin-23 (IL-23) and CD26 engagement drives the acquisition of a cytotoxic program and concurrent loss of the MAIT cell-like phenotype. The ability to modulate the cytotoxic potential of CD26hiCD94lo Vδ2+ cells, combined with their adenosine-binding capacity, may make them ideal targets for immunotherapeutic expansion and adoptive transfer. Wragg et al. identify a population of human gd T cells with striking similarities to MAIT cells. These cells dominate the cord blood Vd2 population and upregulate an effector-like program upon antigen and IL-23 stimulation, providing a potential mechanism by which cytotoxic Vd2 cells may accumulate during adolescence and adulthood. © 2020
- Description: National Health and Medical Research Council, NHMRC
- Authors: Wragg, Kathleen , Tan, Hyon , Kristensen, Anne , Nguyen-Robertson, Catriona , Kelleher, Anthony , Parsons, Matthew , Wheatley, Adam , Berzins, Stuart , Pellicci, Daniel , Kent, Stephen , Juno, Jennifer
- Date: 2020
- Type: Text , Journal article
- Relation: Cell Reports Vol. 31, no. 11 (2020), p.
- Full Text:
- Reviewed:
- Description: Vδ2+ T cells play a critical role in immunity to micro-organisms and cancer but exhibit substantial heterogeneity in humans. Here, we demonstrate that CD26 and CD94 define transcriptionally, phenotypically, and functionally distinct Vδ2+ T cell subsets. Despite distinct antigen specificities, CD26hiCD94lo Vδ2+ cells exhibit substantial similarities to CD26hi mucosal-associated invariant T (MAIT) cells, although CD26− Vδ2+ cells exhibit cytotoxic, effector-like profiles. At birth, the Vδ2+Vγ9+ population is dominated by CD26hiCD94lo cells; during adolescence and adulthood, Vδ2+ cells acquire CD94/NKG2A expression and the relative frequency of the CD26hiCD94lo subset declines. Critically, exposure of the CD26hiCD94lo subset to phosphoantigen in the context of interleukin-23 (IL-23) and CD26 engagement drives the acquisition of a cytotoxic program and concurrent loss of the MAIT cell-like phenotype. The ability to modulate the cytotoxic potential of CD26hiCD94lo Vδ2+ cells, combined with their adenosine-binding capacity, may make them ideal targets for immunotherapeutic expansion and adoptive transfer. Wragg et al. identify a population of human gd T cells with striking similarities to MAIT cells. These cells dominate the cord blood Vd2 population and upregulate an effector-like program upon antigen and IL-23 stimulation, providing a potential mechanism by which cytotoxic Vd2 cells may accumulate during adolescence and adulthood. © 2020
- Description: National Health and Medical Research Council, NHMRC
Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge
- Pellicci, Daniel, Koay, Hui-Fern, Berzins, Stuart
- Authors: Pellicci, Daniel , Koay, Hui-Fern , Berzins, Stuart
- Date: 2020
- Type: Text , Journal article , Review
- Relation: Nature Reviews Immunology Vol. 20, no. 12 (2020), p. 756-770
- Full Text: false
- Reviewed:
- Description: T cell lineages are defined by specialized functions and differential expression of surface antigens, cytokines and transcription factors. Conventional CD4+ and CD8+ T cells are the best studied of the T cell subsets, but ‘unconventional’ T cells have emerged as being more abundant and influential than has previously been appreciated. Key subsets of unconventional T cells include natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells and γδ T cells; collectively, these make up ~10% of circulating T cells, and often they are the majority of T cells in tissues such as the liver and gut mucosa. Defects and deficiencies in unconventional T cells are associated with autoimmunity, chronic inflammation and cancer, so it is important to understand how their development is regulated. In this Review, we describe the thymic development of NKT cells, MAIT cells and γδ T cells and highlight some of the key differences between conventional and unconventional T cell development. © 2020, Springer Nature Limited.
- Koay, Hui-Fern, Su, Shian, Amann-Zalcenstein, Daniela, Daley, Stephen, Comerford, Iain, Miosge, Lisa, Whyte, C. E., Konstantinov, Igor, d'Udekem, Yves, Baldwin, Tracey, Hickey, P. F., Berzins, Stuart, Mak, Jeffrey, Sontani, Yovina, Roots, Carla, Sidwell, Tom, Kallies, Axel, Chen, Zhenjun, Nüssing, S., Kedzierska, Katherine, Mackay, Laura, McColl, Simone, Deenick, Elissa, Fairlie, David, McCluskey, James, Goodnow, Chris, Ritchie, Matthew, Belz, Gabrielle, Naik, Shalin, Pellicci, Daniel, Godfrey, Dale
- Authors: Koay, Hui-Fern , Su, Shian , Amann-Zalcenstein, Daniela , Daley, Stephen , Comerford, Iain , Miosge, Lisa , Whyte, C. E. , Konstantinov, Igor , d'Udekem, Yves , Baldwin, Tracey , Hickey, P. F. , Berzins, Stuart , Mak, Jeffrey , Sontani, Yovina , Roots, Carla , Sidwell, Tom , Kallies, Axel , Chen, Zhenjun , Nüssing, S. , Kedzierska, Katherine , Mackay, Laura , McColl, Simone , Deenick, Elissa , Fairlie, David , McCluskey, James , Goodnow, Chris , Ritchie, Matthew , Belz, Gabrielle , Naik, Shalin , Pellicci, Daniel , Godfrey, Dale
- Date: 2019
- Type: Text , Journal article
- Relation: Science Immunology Vol. 4, no. 41 (2019), p.
- Full Text: false
- Reviewed:
- Description: MR1-restricted mucosal-associated invariant T (MAIT) cells play a unique role in the immune system. These cells develop intrathymically through a three-stage process, but the events that regulate this are largely unknown. Here, using bulk and single-cell RNA sequencing-based transcriptomic analysis in mice and humans, we studied the changing transcriptional landscape that accompanies transition through each stage. Many transcripts were sharply modulated during MAIT cell development, including SLAM (signaling lymphocytic activation molecule) family members, chemokine receptors, and transcription factors. We also demonstrate that stage 3 "mature" MAIT cells comprise distinct subpopulations including newly arrived transitional stage 3 cells, interferon-γ-producing MAIT1 cells and interleukin-17-producing MAIT17 cells. Moreover, the validity and importance of several transcripts detected in this study are directly demonstrated using specific mutant mice. For example, MAIT cell intrathymic maturation was found to be halted in SLAM-associated protein (SAP)-deficient and CXCR6-deficient mouse models, providing clear evidence for their role in modulating MAIT cell development. These data underpin a model that maps the changing transcriptional landscape and identifies key factors that regulate the process of MAIT cell differentiation, with many parallels between mice and humans. Copyright © 2019 The Authors.
Divergent SATB1 expression across human life span and tissue compartments
- Nüssing, Simone, Koay, Hui-Fern, Sant, Sneha, Loudovaris, Thomas, Mannering, Stuart, Lappas, Martha, d′Udekem, Yves, Konstantinov, Igor, Berzins, Stuart, Rimmelzwaan, Guus, Turner, Stephen, Clemens, Bridie, Godfrey, Dale, Nguyen, Thi, Kedzierska, Katherine
- Authors: Nüssing, Simone , Koay, Hui-Fern , Sant, Sneha , Loudovaris, Thomas , Mannering, Stuart , Lappas, Martha , d′Udekem, Yves , Konstantinov, Igor , Berzins, Stuart , Rimmelzwaan, Guus , Turner, Stephen , Clemens, Bridie , Godfrey, Dale , Nguyen, Thi , Kedzierska, Katherine
- Date: 2019
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 97, no. (2019), p. 498-511
- Full Text:
- Reviewed:
- Description: Special AT-rich binding protein-1 (SATB1) is a global chromatin organizer capable of activating or repressing gene transcription in mice and humans. The role of SATB1 is pivotal for T-cell development, with SATB1-knockout mice being neonatally lethal, although the exact mechanism is unknown. Moreover, SATB1 is dysregulated in T-cell lymphoma and proposed to suppress transcription of the Pdcd1 gene, encoding the immune checkpoint programmed cell death protein 1 (PD-1). Thus, SATB1 expression in T-cell subsets across different tissue compartments in humans is of potential importance for targeting PD-1. Here, we comprehensively analyzed SATB1 expression across different human tissues and immune compartments by flow cytometry and correlated this with PD-1 expression. We investigated SATB1 protein levels in pediatric and adult donors and assessed expression dynamics of this chromatin organizer across different immune cell subsets in human organs, as well as in antigen-specific T cells directed against acute and chronic viral infections. Our data demonstrate that SATB1 expression in humans is the highest in T-cell progenitors in the thymus, and then becomes downregulated in mature T cells in the periphery. Importantly, SATB1 expression in peripheral mature T cells is not static and follows fine-tuned expression dynamics, which appear to be tissue- and antigen-dependent. Furthermore, SATB1 expression negatively correlates with PD-1 expression in virus-specific CD8 + T cells. Our study has implications for understanding the role of SATB1 in human health and disease and suggests an approach for modulating PD-1 in T cells, highly relevant to human malignancies or chronic viral infections.
- Authors: Nüssing, Simone , Koay, Hui-Fern , Sant, Sneha , Loudovaris, Thomas , Mannering, Stuart , Lappas, Martha , d′Udekem, Yves , Konstantinov, Igor , Berzins, Stuart , Rimmelzwaan, Guus , Turner, Stephen , Clemens, Bridie , Godfrey, Dale , Nguyen, Thi , Kedzierska, Katherine
- Date: 2019
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 97, no. (2019), p. 498-511
- Full Text:
- Reviewed:
- Description: Special AT-rich binding protein-1 (SATB1) is a global chromatin organizer capable of activating or repressing gene transcription in mice and humans. The role of SATB1 is pivotal for T-cell development, with SATB1-knockout mice being neonatally lethal, although the exact mechanism is unknown. Moreover, SATB1 is dysregulated in T-cell lymphoma and proposed to suppress transcription of the Pdcd1 gene, encoding the immune checkpoint programmed cell death protein 1 (PD-1). Thus, SATB1 expression in T-cell subsets across different tissue compartments in humans is of potential importance for targeting PD-1. Here, we comprehensively analyzed SATB1 expression across different human tissues and immune compartments by flow cytometry and correlated this with PD-1 expression. We investigated SATB1 protein levels in pediatric and adult donors and assessed expression dynamics of this chromatin organizer across different immune cell subsets in human organs, as well as in antigen-specific T cells directed against acute and chronic viral infections. Our data demonstrate that SATB1 expression in humans is the highest in T-cell progenitors in the thymus, and then becomes downregulated in mature T cells in the periphery. Importantly, SATB1 expression in peripheral mature T cells is not static and follows fine-tuned expression dynamics, which appear to be tissue- and antigen-dependent. Furthermore, SATB1 expression negatively correlates with PD-1 expression in virus-specific CD8 + T cells. Our study has implications for understanding the role of SATB1 in human health and disease and suggests an approach for modulating PD-1 in T cells, highly relevant to human malignancies or chronic viral infections.
A potentially important role for T cells and regulatory T cells in Langerhans cell histiocytosis
- Mitchell, Jenée, Berzins, Stuart, Kannourakis, George
- Authors: Mitchell, Jenée , Berzins, Stuart , Kannourakis, George
- Date: 2018
- Type: Text , Journal article , Review
- Relation: Clinical Immunology Vol. 194, no. (2018), p. 19-25
- Full Text: false
- Reviewed:
- Description: Langerhans cell histiocytosis is characterized by lesions containing inflammatory immune cells, including myeloid cells and T cells. Patient mortality remains unacceptably high and new treatment options are required. Several LCH studies have identified aberrant frequencies of T cell subsets with potential immune regulatory properties. High numbers of Foxp3+ regulatory T cells and gamma-delta T cells have been reported in patients with LCH, although, the cause of their presence or their significance is not yet clear. This review describes the current understanding of how LCH develops and progresses, focusing on the growing evidence that regulatory T cell subsets may be important and discussing the exciting potential for harnessing these cells to treat LCH using immune based therapies.
Altered populations of unconventional T Cell lineages in patients with Langerhans Cell Histiocytosis
- Mitchell, Jenée, Kvedaraite, Egle, von Bahr Greenwood, Tatiana, Henter, Jan-Inge, Pellicci, Daniel, Berzins, Stuart, Kannourakis, George
- Authors: Mitchell, Jenée , Kvedaraite, Egle , von Bahr Greenwood, Tatiana , Henter, Jan-Inge , Pellicci, Daniel , Berzins, Stuart , Kannourakis, George
- Date: 2018
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 8, no. 1 (2018), p. 1-13
- Full Text:
- Reviewed:
- Description: Langerhans cell histiocytosis (LCH) lesions are defined by the presence of CD1a+/CD207+ myeloid cells, but many other immune cells are present including unconventional T cells, which have powerful immunoregulatory functions. Unconventional T cell lineages include mucosal-associated invariant T (MAIT) cells, type I natural killer T (NKT) cells and gamma-delta (γδ) T cells, which are associated with many inflammatory conditions, although their importance has not been studied in LCH. We characterized their phenotype and function in blood and lesions from patients with LCH, and identified a deficiency in MAIT cell frequency and abnormalities in the subset distributions of γδ T cells and NKT cells. Such abnormalities are associated with immune dysregulation in other disease settings and are therefore potentially important in LCH. Our study is the first to recognize alterations to MAIT cell proportions in patients with LCH. This finding along with other abnormalities identified amongst unconventional T cells could potentially influence the onset and progression of LCH, thereby highlighting potential targets for new immune based therapies.
Altered populations of unconventional T Cell lineages in patients with Langerhans Cell Histiocytosis
- Authors: Mitchell, Jenée , Kvedaraite, Egle , von Bahr Greenwood, Tatiana , Henter, Jan-Inge , Pellicci, Daniel , Berzins, Stuart , Kannourakis, George
- Date: 2018
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 8, no. 1 (2018), p. 1-13
- Full Text:
- Reviewed:
- Description: Langerhans cell histiocytosis (LCH) lesions are defined by the presence of CD1a+/CD207+ myeloid cells, but many other immune cells are present including unconventional T cells, which have powerful immunoregulatory functions. Unconventional T cell lineages include mucosal-associated invariant T (MAIT) cells, type I natural killer T (NKT) cells and gamma-delta (γδ) T cells, which are associated with many inflammatory conditions, although their importance has not been studied in LCH. We characterized their phenotype and function in blood and lesions from patients with LCH, and identified a deficiency in MAIT cell frequency and abnormalities in the subset distributions of γδ T cells and NKT cells. Such abnormalities are associated with immune dysregulation in other disease settings and are therefore potentially important in LCH. Our study is the first to recognize alterations to MAIT cell proportions in patients with LCH. This finding along with other abnormalities identified amongst unconventional T cells could potentially influence the onset and progression of LCH, thereby highlighting potential targets for new immune based therapies.