Mitochondrial Oxidative Damage Underlies Regulatory T Cell Defects in Autoimmunity

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2020 Aug 2

PMID 32738205

Citations 63

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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