Glucocorticoid Receptor Signaling in Myeloid Cells Orchestrates Inflammation Resolution and Muscle Repair.

Fiche publication

Date publication

septembre 2026

Journal

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Auteurs

Membres identifiés du Cancéropôle Est :
Dr METZGER Daniel , Mr MORLET Bastien , Dr DUTEIL Delphine

Tous les auteurs :
Souali-Crespo S, Rizk JG, Calvano E, Sahu R, Colovic E, Chabba I, Gilbart V, Grandgirard E, Morlet B, Cai Q, Metzger D, Duteil D

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/42733273

Résumé

Glucocorticoids are key regulators of inflammation and tissue repair, yet their precise role in muscle regeneration remains incompletely understood. Here, we investigate the impact of myeloid-specific glucocorticoid receptor (GR) invalidation on macrophage dynamics and muscle stem cell function following acute injury. We demonstrate that the loss of GR in myeloid cells leads to increased macrophage accumulation, driven by altered proliferation and recruitment, without affecting fibro-adipogenic progenitor differentiation or satellite cell proliferation and differentiation under steady-state conditions. Transcriptomic and cistrome analyses at early regeneration stages reveal that GR directly regulates gene networks involved in cell cycle control in myeloid cells. Importantly, administration of dexamethasone during the pro-inflammatory phase markedly delays muscle regeneration by impairing monocyte-to-macrophage transition and promoting macrophage proliferation in a myeloid-GR-dependent manner, ultimately reducing satellite cell proliferation and myogenesis. In contrast, dexamethasone treatment during the anti-inflammatory phase exerts limited effects on muscle recovery. Together, our findings uncover a critical temporal role of GR signaling in myeloid cells in coordinating inflammatory resolution and stem cell function during muscle repair, and highlight the complexity of glucocorticoid actions in regenerative contexts.