Two regulatory T cell populations in the visceral adipose tissue shape systemic metabolism

Torres, SV; Man, K; Elmzzahi, T; Malko, D; Chisanga, D; Liao, Y; Prout, M; Abbott, CA; Tang, A; Wu, J; Becker, M; Mason, T; Haynes, V; Tsui, C; Shakiba, MH; Hamada, D; Britt, K; Groom, JR; McColl, SR; Shi, W; Watt, MJ; Le Gros, G; Pal, B; Beyer, M; Vasanthakumar, A; Kallies, A

Author(s): Torres, SV; Man, K; Elmzzahi, T; Malko, D; Chisanga, D; Liao, Y; Prout, M; Abbott, CA; Tang, A; Wu, J; Becker, M; Mason, T; Haynes, V; Tsui, C; Shakiba, MH; Hamada, D; Britt, K; Groom, JR; McColl, SR; Shi, W; Watt, MJ; Le Gros, G; Pal, B; Beyer, M; Vasanthakumar, A; Kallies, A;
Details: Publication Year 2024-02-14,Volume 25,Issue #3,Page 496-511
Journal Title: Nature Immunology
Abstract: Visceral adipose tissue (VAT) is an energy store and endocrine organ critical for metabolic homeostasis. Regulatory T (T(reg)) cells restrain inflammation to preserve VAT homeostasis and glucose tolerance. Here, we show that the VAT harbors two distinct T(reg) cell populations: prototypical serum stimulation 2-positive (ST2(+)) T(reg) cells that are enriched in males and a previously uncharacterized population of C-X-C motif chemokine receptor 3-positive (CXCR3(+)) T(reg) cells that are enriched in females. We show that the transcription factors GATA-binding protein 3 and peroxisome proliferator-activated receptor-γ, together with the cytokine interleukin-33, promote the differentiation of ST2(+) VAT T(reg) cells but repress CXCR3(+) T(reg) cells. Conversely, the differentiation of CXCR3(+) T(reg) cells is mediated by the cytokine interferon-γ and the transcription factor T-bet, which also antagonize ST2(+) T(reg) cells. Finally, we demonstrate that ST2(+) T(reg) cells preserve glucose homeostasis, whereas CXCR3(+) T(reg) cells restrain inflammation in lean VAT and prevent glucose intolerance under high-fat diet conditions. Overall, this study defines two molecularly and developmentally distinct VAT T(reg) cell types with unique context- and sex-specific functions.
Publisher: NPG
Keywords: Female; Male; Humans; *T-Lymphocytes, Regulatory; *Interleukin-1 Receptor-Like 1 Protein; Intra-Abdominal Fat; Cytokines; Inflammation; Glucose
Research Division(s): Immunology
PubMed ID: 38356058
Publisher's Version: https://doi.org/10.1038/s41590-024-01753-9
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-02-29 09:16:19

Last Modified: 2024-03-11 09:39:16