IL-7Rα signaling in regulatory T cells of adipose tissue is essential for systemic glucose homeostasis

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  • Shinya Abe
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto,
  • Shizue Tani-ichi
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto,
  • Hitoshi Miyachi
    Reproductive Engineering Team, Institute for Life and Medical Sciences, Kyoto University , Kyoto,
  • Satsuki Kitano
    Reproductive Engineering Team, Institute for Life and Medical Sciences, Kyoto University , Kyoto,
  • Akihiro Shimba
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto,
  • Aki Ejima
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto,
  • Takahiro Hara
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto,
  • Guangwei Cui
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto,
  • Tomonobu Kado
    First Department of Internal Medicine, Faculty of Medicine, University of Toyama , Toyama,
  • Shohei Hori
    Laboratory of Immunology and Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo , Tokyo,
  • Kazuyuki Tobe
    Research Center for Pre-Disease Science, Faculty of Medicine, University of Toyama , Toyama,
  • Koichi Ikuta
    Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto,

Bibliographic Information

Published
2025-03-19
Resource Type
journal article
Rights Information
  • https://academic.oup.com/pages/standard-publication-reuse-rights
DOI
  • 10.1093/jimmun/vkae064
Publisher
Oxford University Press (OUP)

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<jats:title>Abstract</jats:title> <jats:p>Regulatory T cells (Tregs) mediate tissue homeostasis and repair. The function of the interleukin-7 receptor α (IL-7Rα) in nonlymphoid tissue Tregs is still unknown, although low expression of IL-7Rα is a widely accepted marker for Tregs. Here, we show that IL-33R (ST2)–expressing Tregs in the visceral adipose tissue (VAT) express the IL-7Rα at high levels. Treg-specific IL-7Rα–deficient mice exhibited reduced adipose ST2+ Tregs and impaired glucose tolerance, whereas IL-7Rα was dispensable for Tregs in lymphoid tissues. Mice deficient in thymic stromal lymphopoietin (TSLP), an additional ligand for IL-7Rα, displayed a modest decrease in adipose ST2+ Tregs and a reduced accumulation of adipose eosinophils, accompanied by slightly impaired glucose tolerance. In the VAT, mesothelial cells expressed IL-7, whereas adipose stem cells and folate receptor β–expressing tissue-resident macrophages expressed TSLP. Thus, this study indicates the significance of IL-7Rα signaling in the maintenance of VAT Tregs and glucose homeostasis, revealing a novel role for IL-7 and TSLP in immunometabolism.</jats:p>

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