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

期刊论文
发表日期：

2024年2月14日

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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

摘要

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.