TY  - JOUR
AU  - Torres, Santiago Valle
AU  - Man, Kevin
AU  - Elmzzahi, Tarek
AU  - Malko, Darya
AU  - Chisanga, David
AU  - Liao, Yang
AU  - Prout, Melanie
AU  - Abbott, Caitlin A
AU  - Tang, Adelynn
AU  - Wu, Jian
AU  - Becker, Matthias Kai Holger
AU  - Mason, Teisha
AU  - Haynes, Vanessa
AU  - Tsui, Carlson
AU  - Hadaddzadeh Shakiba, Mehrnoush
AU  - Hamada, Doaa
AU  - Britt, Kara
AU  - Groom, Joanna R
AU  - McColl, Shaun R
AU  - Shi, Wei
AU  - Watt, Matthew J
AU  - Le Gros, Graham
AU  - Pal, Bhupinder
AU  - Beyer, Marc-Daniel
AU  - Vasanthakumar, Ajithkumar
AU  - Kallies, Axel
TI  - Two regulatory T cell populations in the visceral adipose tissue shape systemic metabolism.
JO  - Nature immunology
VL  - 25
IS  - 3
SN  - 1529-2908
CY  - London
PB  - Springer Nature Limited
M1  - DZNE-2024-00241
SP  - 496 - 511
PY  - 2024
AB  - 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.
KW  - Female
KW  - Male
KW  - Humans
KW  - T-Lymphocytes, Regulatory
KW  - Interleukin-1 Receptor-Like 1 Protein
KW  - Intra-Abdominal Fat
KW  - Cytokines
KW  - Inflammation
KW  - Glucose
KW  - Interleukin-1 Receptor-Like 1 Protein (NLM Chemicals)
KW  - Cytokines (NLM Chemicals)
KW  - Glucose (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38356058
DO  - DOI:10.1038/s41590-024-01753-9
UR  - https://pub.dzne.de/record/268495
ER  -