Tuning macrophage phenotype to mitigate skeletal muscle fibrosis

David M. Stepien, Charles Hwang, Simone Marini, Chase A. Pagani, Michael Sorkin, Noelle D. Visser, Amanda K. Huber, Nicole J. Edwards, Shawn J. Loder, Kaetlin Vasquez, Carlos A. Aguilar, Ravi Kumar, Shamik Mascharak, Michael T. Longaker, Jun Li, Benjamin Levi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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-b1 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-b1 is responsible for the development of traumatic muscle fibrosis, and its blockade offers a promising therapeutic target for preventing muscle fibrosis after ischemic injury.

Original languageEnglish
Pages (from-to)2203-2215
Number of pages13
JournalJournal of Immunology
Issue number8
StatePublished - 15 Apr 2020
Externally publishedYes


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