The CD27/CD70 pathway negatively regulates visceral adipose tissue-resident Th2 cells and controls metabolic homeostasis

作者：Kevin Englebert, Anaëlle Taquin, Abdulkader Azouz, Valérie Acolty, Sylvie Vande Velde, Marie Vanhollebeke, Hadrien Innes, Louis Boon, Tibor Keler, Oberdan Léo, Stanislas Goriely, Muriel Moser, Guillaume Oldenhove · 发表于：Cell Reports · 年份：2024 · DOI：10.1016/j.celrep.2024.113824 · 被引用次数：4 · 研究领域：IL-33, ST2, and ILC Pathways、Immune Cell Function and Interaction、Asthma and respiratory diseases

Adipose tissue homeostasis relies on the interplay between several regulatory lineages, such as type 2 innate lymphoid cells (ILC2s), T helper 2 (Th2) cells, regulatory T cells, eosinophils, and type 2 macrophages. Among them, ILC2s are numerically the dominant source of type 2 cytokines and are considered as major regulators of adiposity. Despite the overlap in immune effector molecules and sensitivity to alarmins (thymic stromal lymphopoietin and interleukin-33) between ILC2s and resident memory Th2 lymphocytes, the role of the adaptive axis of type 2 immunity remains unclear. We show that mice deficient in CD27, a member of the tumor necrosis factor receptor superfamily, are more resistant to obesity and associated disorders. A comparative analysis of the CD4 compartment of both strains revealed higher numbers of fat-resident memory Th2 cells in the adipose tissue of CD27 knockout mice, which correlated with decreased programmed cell death protein 1-induced apoptosis. Our data point to a non-redundant role for Th2 lymphocytes in obesogenic conditions.