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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)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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
Keywords Microglial Cells; Gene-expression; Reg Cells; Brain; Cns; System; Quantification; Macrophages; Depletion; Dynamics
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 16, Issue: 1, Pages: , Article Number: 2744 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Research Unit Type 1 Diabetes Immunology (TDI)
Institute of Diabetes and Obesity (IDO)
Institute of Diabetes Research (IDF)
Grants German Center for Diabetes Research (DZD), through the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
DZD
DFG
Wilhelm-Sander-Stiftung
Anni-Hofmann-Stiftung
Verein zur Foerderung von Wissenschaft und Forschung an der Medizinischen Fakultaet der LMU Muenchen
Alexander von Humboldt Foundation
ERC HypoFlam
Helmholtz Alliance ICEMED-Imaging and Curing Environmental Metabolic Diseases
Max Planck Society for Advancement of Science

Research Division at Helmholtz Zentrum Munchen