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

• DOI: 10.1016/j.cmet.2023.08.010
• Publication Date: 2023-09-20T15:06:21Z
• Authors: Maike Becker; Sini S. Joseph; Francisco Garcia-...; Robby Z. Tom; Daria Opaleva; Isabelle Serr; Matthias H. Tschöp; Tim J. Schulz; Susanna M. Hofmann; Carolin Daniel
• Keywords: Cardiotoxin; Muscle tissue

Muscle-residing regulatory T cells (Tregs) control local tissue integrity and function. However, the molecular interface connecting Treg-based regulation with muscle function regeneration remains largely unexplored. Here, we show that exercise fosters a stable induction of highly functional muscle-residing Tregs increased expression amphiregulin (Areg), EGFR, ST2. Mechanistically, find mice lacking IL6Rα on (TKO) harbor significant reductions in Treg functionality satellite fibro-adipogenic progenitor cells, which are required for regeneration. Using sarcopenia models, TKO demonstrate deficits Tregs, their maturation, more pronounced decline mass. Muscle injury models indicate have disabilities gain restores impaired repair mice. Of note, pharmacological IL6R blockade WT phenocopies identified mice, thereby highlighting clinical implications findings.