TY - JOUR
T1 - Homeostasis and transitional activation of regulatory T cells require c-Myc
AU - Saravia, Jordy
AU - Zeng, Hu
AU - Dhungana, Yogesh
AU - Blanco, Daniel Bastardo
AU - Nguyen, Thanh Long M.
AU - Chapman, Nicole M.
AU - Wang, Yanyan
AU - Kanneganti, Apurva
AU - Liu, Shaofeng
AU - Raynor, Jana L.
AU - Vogel, Peter
AU - Neale, Geoffrey
AU - Carmeliet, Peter
AU - Chi, Hongbo
N1 - Publisher Copyright:
Copyright © 2020 The Authors.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Regulatory T cell (Treg) activation and expansion occur during neonatal life and inflammation to establish immunosuppression, yet the mechanisms governing these events are incompletely understood. We report that the transcriptional regulator c-Myc (Myc) controls immune homeostasis through regulation of Treg accumulation and functional activation. Myc activity is enriched in Tregs generated during neonatal life and responding to inflammation. Myc-deficient Tregs show defects in accumulation and ability to transition to an activated state. Consequently, loss of Myc in Tregs results in an early-onset autoimmune disorder accompanied by uncontrolled effector CD4+ and CD8+ T cell responses. Mechanistically, Myc regulates mitochondrial oxidative metabolism but is dispensable for fatty acid oxidation (FAO). Indeed, Treg-specific deletion of Cox10, which promotes oxidative phosphorylation, but not Cpt1a, the rate-limiting enzyme for FAO, results in impaired Treg function and maturation. Thus, Myc coordinates Treg accumulation, transitional activation, and metabolic programming to orchestrate immune homeostasis.
AB - Regulatory T cell (Treg) activation and expansion occur during neonatal life and inflammation to establish immunosuppression, yet the mechanisms governing these events are incompletely understood. We report that the transcriptional regulator c-Myc (Myc) controls immune homeostasis through regulation of Treg accumulation and functional activation. Myc activity is enriched in Tregs generated during neonatal life and responding to inflammation. Myc-deficient Tregs show defects in accumulation and ability to transition to an activated state. Consequently, loss of Myc in Tregs results in an early-onset autoimmune disorder accompanied by uncontrolled effector CD4+ and CD8+ T cell responses. Mechanistically, Myc regulates mitochondrial oxidative metabolism but is dispensable for fatty acid oxidation (FAO). Indeed, Treg-specific deletion of Cox10, which promotes oxidative phosphorylation, but not Cpt1a, the rate-limiting enzyme for FAO, results in impaired Treg function and maturation. Thus, Myc coordinates Treg accumulation, transitional activation, and metabolic programming to orchestrate immune homeostasis.
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U2 - 10.1126/sciadv.aaw6443
DO - 10.1126/sciadv.aaw6443
M3 - Article
C2 - 31911938
AN - SCOPUS:85077697151
SN - 2375-2548
VL - 6
JO - Science Advances
JF - Science Advances
IS - 1
M1 - eaaw6443
ER -