Showing items 1 - 20 of 43

A divergent transcriptional landscape underpins the development and functional branching of MAIT cells

- 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

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
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  • 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

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
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  • 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.

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.

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

A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage

- Koay, Hui-Fern, Gherardin, Nicholas, Enders, Anselm, Loh, Liyen, Mackay, Laura, Almeida, Catarina, Russ, Brendan, Nold-Petry, Claudia, Nold, Marcel, Bedoui, Sammy, Chen, Zhenjun, Corbett, Alexandra, Eckle, Sidonia, Meehan, Bronwyn, d'Udekem, Yves, Konstantinov, Igor, Lappas, Martha, Liu, Ligong, Goodnow, Chris, Fairlie, David, Rossjohn, Jamie, Chong, Mark, Kedzierska, Katherine, Berzins, Stuart, Belz, Gabrielle, McCluskey, James, Uldrich, Adam, Godfrey, Dale, Pellicci, Daniel

Acute exercise leads to regulation of Telomere-Associated genes and MicroRNA expression in immune Cells

- Chilton, Warrick, Marques, Francine, West, Jenny, Kannourakis, George, Berzins, Stuart, O'Brien, Brendan, Charchar, Fadi

  • Authors: Chilton, Warrick , Marques, Francine , West, Jenny , Kannourakis, George , Berzins, Stuart , O'Brien, Brendan , Charchar, Fadi
  • Date: 2014
  • Type: Text , Journal article
  • Relation: PloS One Vol. 9, no. 4 (2014), p. e92088
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  • Description: Telomeres are specialized nucleoprotein structures that protect chromosomal ends from degradation. These structures progressively shorten during cellular division and can signal replicative senescence below a critical length. Telomere length is predominantly maintained by the enzyme telomerase. Significant decreases in telomere length and telomerase activity are associated with a host of chronic diseases; conversely their maintenance underpins the optimal function of the adaptive immune system. Habitual physical activity is associated with longer leukocyte telomere length; however, the precise mechanisms are unclear. Potential hypotheses include regulation of telomeric gene transcription and/or microRNAs (miRNAs). We investigated the acute exercise-induced response of telomeric genes and miRNAs in twenty-two healthy males (mean age = 24.1±1.55 years). Participants undertook 30 minutes of treadmill running at 80% of peak oxygen uptake. Blood samples were taken before exercise, immediately post-exercise and 60 minutes post-exercise. Total RNA from white blood cells was submitted to miRNA arrays and telomere extension mRNA array. Results were individually validated in white blood cells and sorted T cell lymphocyte subsets using quantitative real-time PCR (qPCR). Telomerase reverse transcriptase (TERT) mRNA (P = 0.001) and sirtuin-6 (SIRT6) (P<0.05) mRNA expression were upregulated in white blood cells after exercise. Fifty-six miRNAs were also differentially regulated post-exercise (FDR <0.05). In silico analysis identified four miRNAs (miR-186, miR-181, miR-15a and miR-96) that potentially targeted telomeric gene mRNA. The four miRNAs exhibited significant upregulation 60 minutes post-exercise (P<0.001). Telomeric repeat binding factor 2, interacting protein (TERF2IP) was identified as a potential binding target for miR-186 and miR-96 and demonstrated concomitant downregulation (P<0.01) at the corresponding time point. Intense cardiorespiratory exercise was sufficient to differentially regulate key telomeric genes and miRNAs in white blood cells. These results may provide a mechanistic insight into telomere homeostasis and improved immune function and physical health. Funding NHMRC

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
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  • 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.

An emerging role for immune regulatory subsets in chronic lymphocytic leukaemia

- Wallace, Morgan, Alcantara, Marice, Minoda, Yosuke, Kannourakis, George, Berzins, Stuart

  • Authors: Wallace, Morgan , Alcantara, Marice , Minoda, Yosuke , Kannourakis, George , Berzins, Stuart
  • Date: 2015
  • Type: Text , Journal article
  • Relation: International Immunopharmacology Vol. 28, no. 2 (2015), p. 897-900
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  • Description: The last few years has seen the burgeoning of a new category of therapeutics for cancer targeting immune regulatory pathways. Antibodies that block the PD-1/PD-L1 interaction are perhaps the most prominent of these new anti-cancer therapies, but several other inhibitory receptor ligand interactions have also shown promise as targets in clinical trials, including CTLA-4/CD80 and Lag-3/MHC class II. Related to this is a rapidly improving knowledge of 'regulatory' lymphocyte lineages, including NKT cells, MATT cells, B regulatory cells and others. These cells have potent cytokine responses that can influence the functioning of other immune cells and many researchers believe that they could be effective targets for therapies designed to enhance immune responses to cancer. This review will outline our current understanding of FOXP3 + 'Tregs', NKT cells, MAIT cells and B regulatory cells immune regulatory cell populations in cancer, with a particular focus on chronic lymphocytic leukaemia (CLL). We will discuss evidence linking CLL with immune regulatory dysfunction and the potential for new therapies targeting regulatory cells. (C) 2015 Elsevier B.V. All rights reserved.

An NZW-derived interval on chromosome 7 moderates sialadenitis, but not insulitis in congenic nonobese diabetic mice

- Burt, Rachel, Watkins, Laura, Tan, Iris, Wang, Nancy, Quirk, Fiona, Mackin, Leanne, Morgan, Phillip, Zhang, Jian-Guo, Berzins, Stuart, Morahan, Grant, Brodnicki, Thomas

  • Authors: Burt, Rachel , Watkins, Laura , Tan, Iris , Wang, Nancy , Quirk, Fiona , Mackin, Leanne , Morgan, Phillip , Zhang, Jian-Guo , Berzins, Stuart , Morahan, Grant , Brodnicki, Thomas
  • Date: 2010
  • Type: Text , Journal article
  • Relation: Journal of Immunology Vol. 184, no. 2 (2010), p. 859-868
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  • Description: Autoimmune lymphocytic infiltration of the salivary glands, termed sialadenitis, is a pathologic feature of Sjögren's syndrome (SjS) that is also prominent in nonobese diabetic (NOD) mice. Genetic factors regulate sialadenitis, and a previous (NOD x NZW)F2 study detected linkage to murine chromosome (Chr) 7. The locus, subsequently annotated as Ssial3, maps to the distal end of Chr7 and overlaps a region associated with type 1 diabetes susceptibility in NOD mice. To examine whether Ssial3 could contribute to both diseases, or was specific for SjS, we generated a congenic mouse strain that harbored an NZW-derived Chr7 interval on the NOD genetic background. This congenic strain exhibited reduced sialadenitis compared with NOD mice and confirmed Ssial3. This reduction, however, did not ameliorate saliva abnormalities associated with SjS-like disease in NOD mice, nor were congenic mice protected against insulitis (lymphocytic infiltration of the pancreatic islets) or diabetes onset. Thus, the Ssial3 locus appears to have a tissue-specific effect for which the NZW allele is unable to prevent other autoimmune traits in the NOD mouse. Anomalous increases for antinuclear Ab production and frequency of marginal-zone B cells were also identified in congenic mice, indicating that theNZW-derived Chr7 interval has a complex effect on the NOD immune system. Copyright © 2010 by The American Association of Immunologists, Inc.

Control points in NKT-cell development

- Godfrey, Dale, Berzins, Stuart

  • Authors: Godfrey, Dale , Berzins, Stuart
  • Date: 2007
  • Type: Text , Journal article
  • Relation: Nature Reviews Immunology Vol. 7, no. 7 (July 2007 2007), p. 505-518
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  • Description: CD1d-dependent natural killer T (NKT) cells are a unique T-cell subset with the ability to regulate the immune system in response to a broad range of diseases. That low NKT-cell numbers are associated with many different disease states in mice and humans, combined with the fact that NKT-cell numbers vary widely between individuals, makes it crucial to understand how these cells develop and how their numbers are maintained. Here, we review the current state of knowledge of NKT-cell development and attempt to highlight the most important questions in this field.
  • Description: C1

Developing NKT cells need their (E) protein

- Chan, Angela, Berzins, Stuart, Godfrey, Dale

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

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

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
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  • 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.

Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population

- Coquet, Jonathan, Chakravarti, Sumone, Kyparissoudis, Konstantinos, McNab, Finlay, Pitt, Lauren, McKenzie, Brent, Berzins, Stuart, Smyth, Mark, Godfrey, Dale

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

Ex-vivo analysis of human Natural Killer T cells demonstrates heterogeneity between tissues and within established CD4+ and CD4- subsets

- Chan, Angela, Leeansyah, Edwin, Cochrane, Andrew, d'Udekem, Yves, Mittag, Diana, Harrison, Leonard, Godfrey, Dale, Berzins, Stuart

  • Authors: Chan, Angela , Leeansyah, Edwin , Cochrane, Andrew , d'Udekem, Yves , Mittag, Diana , Harrison, Leonard , Godfrey, Dale , Berzins, Stuart
  • Date: 2013
  • Type: Text , Journal article
  • Relation: Clinical and Experimental Immunology Vol. 172, no. 1 (2013), p. 129-137
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  • Description: Summary: Our understanding of human type 1 natural killer T (NKT) cells has been heavily dependent on studies of cells from peripheral blood. These have identified two functionally distinct subsets defined by expression of CD4, although it is widely believed that this underestimates the true number of subsets. Two recent studies supporting this view have provided more detail about diversity of the human NKT cells, but relied on analysis of NKT cells from human blood that had been expanded in vitro prior to analysis. In this study we extend those findings by assessing the heterogeneity of CD4+ and CD4- human NKT cell subsets from peripheral blood, cord blood, thymus and spleen without prior expansion ex vivo, and identifying for the first time cytokines expressed by human NKT cells from spleen and thymus. Our comparative analysis reveals highly heterogeneous expression of surface antigens by CD4+ and CD4- NKT cell subsets and identifies several antigens whose differential expression correlates with the cytokine response. Collectively, our findings reveal that the common classification of NKT cells into CD4+ and CD4- subsets fails to reflect the diversity of this lineage, and that more studies are needed to establish the functional significance of the antigen expression patterns and tissue residency of human NKT cells. © 2012 British Society for Immunology.
  • Description: 2003010856

Experimental and human evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin NGAL ) in the development of cardiac hypertrophy and heart failure

- Marques, Francine, Prestes, Priscilla, Byars, Sean, Ritchie, Scott, Wurtz, Peter, Patel, Sheila, Booth, Scott, Rana, Indrajeetsinh, Minoda, Yosuke, Berzins, Stuart, Curl, Claire, Bell, James, Wai, Bryan, Srivastava, Piyush, Kangas, Antti, Soininen, Pasi, Ruohonen, Saku, Kahonen, Mika, Lehtimaki, Terho, Raitoharju, Emma, Havulinna, Aki, Perola, Markus, Raitakari, Olli, Salomaa, Veikko, Ala-Korpela, Mika, Kettunen, Johannes, McGlynn, Maree, Kelly, Jason, Wlodek, Mary, Lewandowski, Paul, Delbridge, Lea, Burrell, Louise, Inouye, Michael, Harrap, Stephen, Charchar, Fadi

Foxp3+ tregs from langerhans cell histiocytosis lesions co-express CD56 and have a definitively regulatory capacity

- 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.
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  • 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