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Tuning Macrophage Phenotype to Mitigate Skeletal Muscle Fibrosis. Journal of immunology (Baltimore, Md. : 1950) Stepien, D. M., Hwang, C. n., Marini, S. n., Pagani, C. A., Sorkin, M. n., Visser, N. D., Huber, A. K., Edwards, N. J., Loder, S. J., Vasquez, K. n., Aguilar, C. A., Kumar, R. n., Mascharak, S. n., Longaker, M. T., Li, J. n., Levi, B. n. 2020

Abstract

Myeloid cells are critical to the development of fibrosis following muscle injury; however, the mechanism of their role in fibrosis formation remains unclear. In this study, we demonstrate that myeloid cell-derived TGF-ß1 signaling is increased in a profibrotic ischemia reperfusion and cardiotoxin muscle injury model. We found that myeloid-specific deletion of Tgfb1 abrogates the fibrotic response in this injury model and reduces fibro/adipogenic progenitor cell proliferation while simultaneously enhancing muscle regeneration, which is abrogated by adaptive transfer of normal macrophages. Similarly, a murine TGFBRII-Fc ligand trap administered after injury significantly reduced muscle fibrosis and improved muscle regeneration. This study ultimately demonstrates that infiltrating myeloid cell TGF-ß1 is responsible for the development of traumatic muscle fibrosis, and its blockade offers a promising therapeutic target for preventing muscle fibrosis after ischemic injury.

View details for DOI 10.4049/jimmunol.1900814

View details for PubMedID 32161098