%0 Journal Article
%A Torres, Santiago Valle
%A Man, Kevin
%A Elmzzahi, Tarek
%A Malko, Darya
%A Chisanga, David
%A Liao, Yang
%A Prout, Melanie
%A Abbott, Caitlin A
%A Tang, Adelynn
%A Wu, Jian
%A Becker, Matthias Kai Holger
%A Mason, Teisha
%A Haynes, Vanessa
%A Tsui, Carlson
%A Hadaddzadeh Shakiba, Mehrnoush
%A Hamada, Doaa
%A Britt, Kara
%A Groom, Joanna R
%A McColl, Shaun R
%A Shi, Wei
%A Watt, Matthew J
%A Le Gros, Graham
%A Pal, Bhupinder
%A Beyer, Marc-Daniel
%A Vasanthakumar, Ajithkumar
%A Kallies, Axel
%T Two regulatory T cell populations in the visceral adipose tissue shape systemic metabolism.
%J Nature immunology
%V 25
%N 3
%@ 1529-2908
%C London
%I Springer Nature Limited
%M DZNE-2024-00241
%P 496 - 511
%D 2024
%X Visceral adipose tissue (VAT) is an energy store and endocrine organ critical for metabolic homeostasis. Regulatory T (Treg) cells restrain inflammation to preserve VAT homeostasis and glucose tolerance. Here, we show that the VAT harbors two distinct Treg cell populations: prototypical serum stimulation 2-positive (ST2+) Treg cells that are enriched in males and a previously uncharacterized population of C-X-C motif chemokine receptor 3-positive (CXCR3+) Treg 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 Treg cells but repress CXCR3+ Treg cells. Conversely, the differentiation of CXCR3+ Treg cells is mediated by the cytokine interferon-γ and the transcription factor T-bet, which also antagonize ST2+ Treg cells. Finally, we demonstrate that ST2+ Treg cells preserve glucose homeostasis, whereas CXCR3+ Treg 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 Treg cell types with unique context- and sex-specific functions.
%K Female
%K Male
%K Humans
%K T-Lymphocytes, Regulatory
%K Interleukin-1 Receptor-Like 1 Protein
%K Intra-Abdominal Fat
%K Cytokines
%K Inflammation
%K Glucose
%K Interleukin-1 Receptor-Like 1 Protein (NLM Chemicals)
%K Cytokines (NLM Chemicals)
%K Glucose (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38356058
%R 10.1038/s41590-024-01753-9
%U https://pub.dzne.de/record/268495