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Becker, M. ; Joseph, S.S. ; Garcia-Carrizo, F.* ; Tom, R.Z. ; Opaleva, D. ; Serr, I. ; Tschöp, M.H. ; Schulz, T.* ; Hofmann, S.M. ; Daniel, C.

Regulatory T cells require IL6 receptor alpha signaling to control skeletal muscle function and regeneration.

Cell Metab. 35, 1736-1751.e7 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Muscle-residing regulatory T cells (Tregs) control local tissue integrity and function. However, the molecular interface connecting Treg-based regulation with muscle function and regeneration remains largely unexplored. Here, we show that exercise fosters a stable induction of highly functional muscle-residing Tregs with increased expression of amphiregulin (Areg), EGFR, and ST2. Mechanistically, we find that mice lacking IL6Rα on T cells (TKO) harbor significant reductions in muscle Treg functionality and satellite and fibro-adipogenic progenitor cells, which are required for muscle regeneration. Using exercise and sarcopenia models, IL6Rα TKO mice demonstrate deficits in Tregs, their functional maturation, and a more pronounced decline in muscle mass. Muscle injury models indicate that IL6Rα TKO mice have significant disabilities in muscle regeneration. Treg gain of function restores impaired muscle repair in IL6Rα TKO mice. Of note, pharmacological IL6R blockade in WT mice phenocopies deficits in muscle function identified in IL6Rα TKO mice, thereby highlighting the clinical implications of the findings.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Exercise ; Il6ra Signaling ; Immune Tissue Crosstalk ; Immune-metabolic Crosstalk ; Immunometabolism ; Injury ; Muscle Function ; Niche-specific Tregs ; Tissue Tregs ; Voluntary Wheel Running; Il-6 Receptor; Reg Cells; Growth; Interleukin-6; Expression; Exercise; Stat3; Amphiregulin; Inflammation; Population
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Journal Cell Metabolism
Quellenangaben Volume: 35, Issue: 10, Pages: 1736-1751.e7 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Regeneration Research (IDR)
Type 1 Diabetes Immunology (TDI)
Institute of Diabetes and Obesity (IDO)
Grants Research Group at Helmholtz Zentrum Munchen
German Center for Diabetes Research (DZD)
EFSD/JDRF/Lilly Program on Type 1 Diabetes Research 2020
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Deutsche Forschungsgemeinschaft
Alexander von Humboldt Foundation
Helmholtz Alliance ICEMED
Helmholtz Initiative on Personalized Medicinei Med by the Helmholtz Association
Excellence Program for Outstanding Female Scientists from the Helmholtz Association
European Research Council(ERC)
Helmholtz cross-program topic ''Metabolic Dysfunction''
Initiative and Networking Fund of the Helmholtz Association
German Ministry of Education and Research(BMBF)
State of Brandenburg (DZD)
Core Facility Pathology & Tissue Analytics at Helmholtz Munich