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Becker, M. ; Kälin, S. ; Neubig, A.H. ; Lauber, M. ; Opaleva, D. ; Hipp, H. ; Salb, V.K. ; Ott, V. ; Legutko, B. ; Kälin, R.E.* ; Hippich, M. ; Scherm, M.G. ; Nascimento, L.F.R. ; Serr, I. ; Hosp, F.* ; Nikolaev, A.* ; Mohebiany, A.* ; Krueger, M.* ; Flachmeyer, B.* ; Pfaffl, M.W.* ; Haase, B.* ; Yi, C.X.* ; Dietzen, S.* ; Bopp, T.* ; Woods, S.C.* ; Waisman, A.* ; Weigmann, B.* ; Mann, M.* ; Tschöp, M.H. ; Daniel, C.

Regulatory T cells in the mouse hypothalamus control immune activation and ameliorate metabolic impairments in high-calorie environments.

Nat. Commun. 16:2744 (2025)
DOI PMC
The hypothalamus in the central nervous system (CNS) has important functions in controlling systemic metabolism. A calorie-rich diet triggers CNS immune activation, impairing metabolic control and promoting obesity and Type 2 Diabetes (T2D), but the mechanisms driving hypothalamic immune activation remain unclear. Here we identify regulatory T cells (Tregs) as key modulators of hypothalamic immune responses. In mice, calorie-rich environments activate hypothalamic CD4+ T cells, infiltrating macrophages and microglia while reducing hypothalamic Tregs. mRNA profiling of hypothalamic CD4+ T cells reveals a Th1-like activation state, with increased Tbx21, Cxcr3 and Cd226 but decreased Ccr7 and S1pr1. Importantly, results from Treg loss-of function and gain-of-function experiments show that Tregs limit hypothalamic immune activation and reverse metabolic impairments induced by hyper-caloric feeding. Our findings thus help refine the current model of Treg-centered immune-metabolic crosstalk in the brain and may contribute to the development of precision immune modulation for obesity and diabetes.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 16, Issue: 1, Pages: , Article Number: 2744 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Type 1 Diabetes Immunology (TDI)
Institute of Diabetes and Obesity (IDO)
Institute of Diabetes Research (IDF)