| First Author | Saravia J | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 1 | Pages | eaaw6443 |
| PubMed ID | 31911938 | Mgi Jnum | J:287614 |
| Mgi Id | MGI:6415472 | Doi | 10.1126/sciadv.aaw6443 |
| Citation | Saravia J, et al. (2020) Homeostasis and transitional activation of regulatory T cells require c-Myc. Sci Adv 6(1):eaaw6443 |
| abstractText | 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. |
