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
- Full Text:
- Reviewed:
- 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
- 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
- Full Text:
- Reviewed:
- 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
Does CD1a expression influence T cell function in patients with langerhans cell histiocytosis?
- Mitchell, Jenee, Kannourakis, George
- Authors: Mitchell, Jenee , Kannourakis, George
- Date: 2021
- Type: Text , Journal article
- Relation: Frontiers in Immunology Vol. 12, no. (2021), p.
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- Reviewed:
- Description: Langerhans cell histiocytosis lesions are characterized by CD1a+ myeloid lineage LCH cells and an inflammatory infiltrate of cytokines and immune cells, including T cells. T cells that recognize CD1a may be implicated in the pathology of many disease states including cancer and autoimmunity but have not been studied in the context of LCH despite the expression of CD1a by LCH cells. In this perspective article, we discuss the expression of CD1a by LCH cells, and we explore the potential for T cells that recognize CD1a to be involved in LCH pathogenesis. Copyright © 2021 Mitchell and Kannourakis.
- Authors: Mitchell, Jenee , Kannourakis, George
- Date: 2021
- Type: Text , Journal article
- Relation: Frontiers in Immunology Vol. 12, no. (2021), p.
- Full Text:
- Reviewed:
- Description: Langerhans cell histiocytosis lesions are characterized by CD1a+ myeloid lineage LCH cells and an inflammatory infiltrate of cytokines and immune cells, including T cells. T cells that recognize CD1a may be implicated in the pathology of many disease states including cancer and autoimmunity but have not been studied in the context of LCH despite the expression of CD1a by LCH cells. In this perspective article, we discuss the expression of CD1a by LCH cells, and we explore the potential for T cells that recognize CD1a to be involved in LCH pathogenesis. Copyright © 2021 Mitchell and Kannourakis.
Polyclonal T-Cells Express CD1a in Langerhans Cell Histiocytosis (LCH) Lesions
- West, Jennifer, Olsen, Sharon, Mitchell, Jenée, Priddle, Ross, Luke, Jennifer, Åkefeldt, Selma Olsson, Henter, Jan-Inge, Turville, Christopher, Kannourakis, George
- Authors: West, Jennifer , Olsen, Sharon , Mitchell, Jenée , Priddle, Ross , Luke, Jennifer , Åkefeldt, Selma Olsson , Henter, Jan-Inge , Turville, Christopher , Kannourakis, George
- Date: 2014
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 9, no. 10 (2014), p. 1-12
- Full Text:
- Reviewed:
- Description: Langerhans cell histiocytosis (LCH) is a complex and poorly understood disorder that has characteristics of both inflammatory and neoplastic disease. By using eight-colour flow cytometry, we have identified a previously unreported population of CD1a+/CD3+ T-cells in LCH lesions. The expression of CD1a is regarded as a hallmark of this disease; however, it has always been presumed that it was only expressed by pathogenic Langerhans cells (LCs). We have now detected CD1a expression by a range of T-cell subsets within all of the LCH lesions that were examined, establishing that CD1a expression in these lesions is no longer restricted to pathogenic LCs. The presence of CD1a+ T-cells in all of the LCH lesions that we have studied to date warrants further investigation into their biological function to determine whether these cells are important in the pathogenesis of LCH. [ABSTRACT FROM AUTHOR] Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Authors: West, Jennifer , Olsen, Sharon , Mitchell, Jenée , Priddle, Ross , Luke, Jennifer , Åkefeldt, Selma Olsson , Henter, Jan-Inge , Turville, Christopher , Kannourakis, George
- Date: 2014
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 9, no. 10 (2014), p. 1-12
- Full Text:
- Reviewed:
- Description: Langerhans cell histiocytosis (LCH) is a complex and poorly understood disorder that has characteristics of both inflammatory and neoplastic disease. By using eight-colour flow cytometry, we have identified a previously unreported population of CD1a+/CD3+ T-cells in LCH lesions. The expression of CD1a is regarded as a hallmark of this disease; however, it has always been presumed that it was only expressed by pathogenic Langerhans cells (LCs). We have now detected CD1a expression by a range of T-cell subsets within all of the LCH lesions that were examined, establishing that CD1a expression in these lesions is no longer restricted to pathogenic LCs. The presence of CD1a+ T-cells in all of the LCH lesions that we have studied to date warrants further investigation into their biological function to determine whether these cells are important in the pathogenesis of LCH. [ABSTRACT FROM AUTHOR] Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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