2020
DOI: 10.1016/j.cmet.2020.07.001
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Mitochondrial Oxidative Damage Underlies Regulatory T Cell Defects in Autoimmunity

Abstract: Highlights d Intense metabolic reprogramming of Tregs occurs with autoimmunity d Treg mitochondrial oxidative stress is elevated during EAE d Treg mtROS attenuates lysosomal function, induces a DDR, and promotes cell death d mCAT overexpression prevents Treg death and restores autoimmune responses

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Cited by 99 publications
(92 citation statements)
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“…Mitochondria thus appears to play a pivotal role in immune cell metabolic reprogramming ensuring, as a signaling hub, the adequate crosstalk between immunity control and cellular energy providing (137,(159)(160)(161)(162). To that end, mitochondria transfer is under investigation.…”
Section: Metabolism At the Heart Of Mscs And Immune Cells Crosstalkmentioning
confidence: 99%
“…Mitochondria thus appears to play a pivotal role in immune cell metabolic reprogramming ensuring, as a signaling hub, the adequate crosstalk between immunity control and cellular energy providing (137,(159)(160)(161)(162). To that end, mitochondria transfer is under investigation.…”
Section: Metabolism At the Heart Of Mscs And Immune Cells Crosstalkmentioning
confidence: 99%
“…Treg function alterations associate with MT oxidative stress, dysfunctional mitophagy, and enhanced DNA damage and cell death(103,104). We hypothesized that the expressions of OCRGs are modulated in CD4 + CD25 high FOXP3 + Treg in comparison with those of CD4 + CD25 − T effector cell controls.…”
mentioning
confidence: 99%
“…Similar to CD4+ and CD8+ T cells, the DDR mechanisms in Tregs are receiving increased attention since these cells have a pivotal role in the tumor microenvironment where DNA damage usually precedes, and in preventing autoimmunity where the DDR's role is currently emerging. In a recent study from our team [60], the transcriptomic analysis of Tregs in MS, SLE and RA patients revealed elevated expression levels of DDR-related genes as H2AFx, TP53, CHK2 and TP53BP1. The aberrant DDR was confirmed in an experimental mouse model (EAE) of MS by the increased levels of phospho-ATM (Ser1981), p53BP1 and γH2AX proteins.…”
Section: Linking T Cell Ddr With Autoimmunitymentioning
confidence: 95%