Mitochondrial Oxidative Damage Underlies Regulatory T Cell Defects in Autoimmunity.

Mitochondrial Oxidative Damage Underlies Regulatory T Cell Defects in Autoimmunity.
Cell Metab. 2020 Jul 22;:
Authors: Alissafi T, Kalafati L, Lazari M, Filia A, Kloukina I, Manifava M, Lim JH, Alexaki VI, Ktistakis NT, Doskas T, Garinis GA, Chavakis T, Boumpas DT, Verginis P
Abstract
Regulatory T cells (Tregs) are vital for the maintenance of immune homeostasis, while their dysfunction constitutes a cardinal feature of autoimmunity. Under steady-state conditions, mitochondrial metabolism is critical for Treg function; however, the metabolic adaptations of Tregs during autoimmunity are ill-defined. Herein, we report that elevated mitochondrial oxidative stress and a robust DNA damage response (DDR) associated with cell death occur in Tregs in individuals with autoimmunity. In an experimental autoimmune encephalitis (EAE) mouse model of autoimmunity, we found a Treg dysfunction recapitulating the features of autoimmune Tregs with a prominent mtROS signature. Scavenging of mtROS in Tregs of EAE mice reversed the DDR and prevented Treg death, while attenuating the Th1 and Th17 autoimmune responses. These findings highlight an unrecognized role of mitochondrial oxidative stress in defining Treg fate during autoimmunity, which may facilitate the design of novel immunotherapies for diseases with disturbed immune tolerance.
PMID: 32738205 [PubMed - as supplied by publisher]

Source: Cell Metabolism - July 21, 2020 Category: Cytology Authors: Alissafi T, Kalafati L, Lazari M, Filia A, Kloukina I, Manifava M, Lim JH, Alexaki VI, Ktistakis NT, Doskas T, Garinis GA, Chavakis T, Boumpas DT, Verginis P Tags: Cell Metab Source Type: research