2026-06-14T00:31:38Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/258592025-12-18T13:01:27Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Nikolic, Ivana author Ruiz-Garrido, Irene author Crespo, María author Romero-Becerra, Rafael author Leiva-Vega, Luis author Mora, Alfonso author León, Marta author Rodríguez, Elena author Leiva, Magdalena author Plata-Gómez, Ana Belén author Alvarez Flores, Maria Beatriz author Torres, Jorge L author Hernández-Cosido, Lourdes author López, Juan Antonio author Vázquez, Jesús author Efeyan, Alejo author Martin, Pilar author Marcos, Miguel author Sabio, Guadalupe author 2024-06 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. EMBO Rep. 2024 Jun;25(6):2635-2661. EMBO Reports 38730210 https://hdl.handle.net/20.500.12105/25859 Adipose Tissue Obesity T Regulatory Cells Thermogenesis p38 Stress Kinases Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis.