Two regulatory T cell populations in the visceral adipose tissue shape systemic metabolism
Date
2024
Authors
Torres, S.V.
Man, K.
Elmzzahi, T.
Malko, D.
Chisanga, D.
Liao, Y.
Prout, M.
Abbott, C.A.
Tang, A.
Wu, J.
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Journal article
Citation
Nature Immunology, 2024; 25(3):496-511
Statement of Responsibility
Santiago Valle Torres, Kevin Man, Tarek Elmzzahi, Darya Malko, David Chisanga, Yang Liao, Melanie Prout, Caitlin A. Abbott, Adelynn Tang, Jian Wu, Matthias Becker, Teisha Mason, Vanessa Haynes, Carlson Tsui, Mehrnoush Hadaddzadeh Shakiba, Doaa Hamada, Kara Britt, Joanna R. Groom, Shaun R. McColl, Wei Shi, Matthew J. Watt, Graham Le Gros, Bhupinder Pal, Marc Beyer, Ajithkumar Vasanthakumar, Axel Kallies
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Abstract
Visceral adipose tissue (VAT) is an energy store and endocrine organ critical for metabolic homeostasis. Regulatory T (Treg) cells restrain infammation 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 diferentiation of ST2+ VAT Treg cells but repress CXCR3+ Treg cells. Conversely, the diferentiation 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 infammation in lean VAT and prevent glucose intolerance under high-fat diet conditions. Overall, this study defnes two molecularly and developmentally distinct VAT Treg cell types with unique context- and sex-specifc functions.
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© 2024 Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.