| First Author | Nikolic I | Year | 2024 |
| Journal | EMBO Rep | Volume | 25 |
| Issue | 6 | Pages | 2635-2661 |
| PubMed ID | 38730210 | Mgi Jnum | J:360190 |
| Mgi Id | MGI:7658829 | Doi | 10.1038/s44319-024-00149-y |
| Citation | Nikolic I, et al. (2024) Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis. EMBO Rep 25(6):2635-2661 |
| abstractText | Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8(+) T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function. |
