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Immunol."],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by an inexorable decline in lung function with limited treatment options. The abnormal expression of transforming growth factor-\u03b2 (TGF-\u03b2) in profibrotic macrophages is linked to severe pulmonary fibrosis, but the regulation mechanisms of TGF-\u03b2 expression are incompletely understood. We found that decreased expression of E3 ubiquitin ligase <jats:italic>Fbxw7<\/jats:italic> in peripheral blood mononuclear cells (PBMCs) was significantly related to the severity of pulmonary fibrosis in IPF patients. Fbxw7 is identified to be a crucial suppressing factor for pulmonary fibrosis development and progression in a mouse model induced by intratracheal bleomycin treatment. Myeloid cell-specific <jats:italic>Fbxw7<\/jats:italic> deletion increases pulmonary monocyte-macrophages accumulation in lung tissue, and eventually promotes bleomycin-induced collagen deposition and progressive pulmonary fibrosis. Notably, the expression of TGF-\u03b2 in profibrotic macrophages was significantly upregulated in myeloid cell-specific <jats:italic>Fbxw7<\/jats:italic> deletion mice after bleomycin treatment. C-Jun has long been regarded as a critical transcription factor of <jats:italic>Tgfb1<\/jats:italic>, we clarified that Fbxw7 inhibits the expression of TGF-\u03b2 in profibrotic macrophages by interacting with c-Jun and mediating its K48-linked ubiquitination and degradation. These findings provide insight into the role of Fbxw7 in the regulation of macrophages during the pathogenesis of pulmonary fibrosis.<\/jats:p>","DOI":"10.3389\/fimmu.2021.760138","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T08:37:26Z","timestamp":1641371846000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Myeloid Fbxw7 Prevents Pulmonary Fibrosis by Suppressing TGF-\u03b2 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