Journal Article

DZNE-2024-00241

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Two regulatory T cell populations in the visceral adipose tissue shape systemic metabolism.

Torres, S. V. ; Man, K. ; Elmzzahi, T.DZNE* ; Malko, D.DZNE* ; Chisanga, D. ; Liao, Y. ; Prout, M. ; Abbott, C. A. ; Tang, A. ; Wu, J. ; Becker, M. K. H.DZNE* ; Mason, T. ; Haynes, V. ; Tsui, C. ; Hadaddzadeh Shakiba, M.DZNE* ; Hamada, D.DZNE* ; Britt, K. ; Groom, J. R. ; McColl, S. R. ; Shi, W. ; Watt, M. J. ; Le Gros, G. ; Pal, B. ; Beyer, M.-D.DZNE* ; Vasanthakumar, A. ; Kallies, A.

2024
Springer Nature Limited London

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Please use a persistent id in citations: doi:10.1038/s41590-024-01753-9

Abstract: 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.

Keyword(s): Female (MeSH) ; Male (MeSH) ; Humans (MeSH) ; T-Lymphocytes, Regulatory (MeSH) ; Interleukin-1 Receptor-Like 1 Protein (MeSH) ; Intra-Abdominal Fat (MeSH) ; Cytokines (MeSH) ; Inflammation (MeSH) ; Glucose (MeSH) ; Interleukin-1 Receptor-Like 1 Protein ; Cytokines ; Glucose

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Contributing Institute(s):

1. Immunogenomics and Neurodegeneration (AG Beyer)
2. Modular High Performance Computing and Artificial Intelligence (AG Becker)
3. Platform for Single Cell Genomics and Epigenomics (PRECISE)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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