Fig. 3: The underlying mechanism of Treg in skeletal muscle repair and regeneration.
From: Regulatory T cells in skeletal muscle repair and regeneration: recent insights
After muscle injury, mMSCs secrete IL-33 which binds to ST receptors on Tregs causing Treg aggregation at the damaged site. IFN-γ produced by effector T cells causes polarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages and promotes the proliferation of satellite cells to facilitate tissue repair. Tregs also secrete Areg to influence the repair process by directly promoting the proliferation of satellite cells through the EGFR pathway. Areg inhibits Treg-regulated T cell differentiation to Th1 cells, thereby suppressing the local inflammatory response. Estrogen inhibits Th1 responses in damaged muscle by promoting Treg cell aggregation, thereby reducing inflammation in skeletal muscle. PD-1 downregulation affects Treg aggregation in skeletal muscle and impairs skeletal muscle regeneration, whereas CCL2 may potentially regulate Treg aggregation to affect the repair process. mMscs, muscle mesenchymal stem cells; CGRP, calcitonin gene related peptide; CCL2, chemokine ligand 2; IFN-γ, interferon-γ; Teff, effector T cell; NK cell, natural killer cell; Th1, T-helper 1 cell; EGFR, epidermal growth factor receptor; PD-1, programmed cell death ligand 1.
