Homeostasis and transitional activation of regulatory T cells require c-Myc

Jordy Saravia, Hu Zeng, Yogesh Dhungana, Daniel Bastardo Blanco, Thanh Long M. Nguyen, Nicole M. Chapman, Yanyan Wang, Apurva Kanneganti, Shaofeng Liu, Jana L. Raynor, Peter Vogel, Geoffrey Neale, Peter Carmeliet, Hongbo Chi

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2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbereaaw6443
JournalScience Advances
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

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    Saravia, J., Zeng, H., Dhungana, Y., Blanco, D. B., Nguyen, T. L. M., Chapman, N. M., Wang, Y., Kanneganti, A., Liu, S., Raynor, J. L., Vogel, P., Neale, G., Carmeliet, P., & Chi, H. (2020). Homeostasis and transitional activation of regulatory T cells require c-Myc. Science Advances, 6(1), [eaaw6443]. https://doi.org/10.1126/sciadv.aaw6443