小柯机器人

希腊雅典学院Panayotis Verginis、Themis Alissafi等研究人员合作发现，线粒体氧化损伤导致自身免疫中的调节性T细胞缺陷。该项研究成果于2020年7月31日在线发表在《细胞—代谢》杂志上。

Title: Mitochondrial Oxidative Damage Underlies Regulatory T Cell Defects in Autoimmunity

Author: Themis Alissafi, Lydia Kalafati, Maria Lazari, Anastasia Filia, Ismini Kloukina, Maria Manifava, Jong-Hyung Lim, Vasileia Ismini Alexaki, Nicholas T. Ktistakis, Triantafyllos Doskas, George A. Garinis, Triantafyllos Chavakis, Dimitrios T. Boumpas, Panayotis Verginis

Issue&Volume: 2020-07-31

Abstract: Regulatory T cells (Tregs) are vital for the maintenance of immune homeostasis, whiletheir dysfunction constitutes a cardinal feature of autoimmunity. Under steady-stateconditions, mitochondrial metabolism is critical for Treg function; however, the metabolicadaptations of Tregs during autoimmunity are ill-defined. Herein, we report that elevatedmitochondrial oxidative stress and a robust DNA damage response (DDR) associated withcell death occur in Tregs in individuals with autoimmunity. In an experimental autoimmuneencephalitis (EAE) mouse model of autoimmunity, we found a Treg dysfunction recapitulatingthe features of autoimmune Tregs with a prominent mtROS signature. Scavenging of mtROSin Tregs of EAE mice reversed the DDR and prevented Treg death, while attenuatingthe Th1 and Th17 autoimmune responses. These findings highlight an unrecognized roleof mitochondrial oxidative stress in defining Treg fate during autoimmunity, whichmay facilitate the design of novel immunotherapies for diseases with disturbed immunetolerance.

DOI: 10.1016/j.cmet.2020.07.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30359-4

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