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TGF-\u03b2 is a crucial mediator of persistent myofibroblast activation and aberrant extracellular matrix production in SSc. The factors responsible for this are unknown. By amplifying pattern recognition receptor signaling, triggering receptor expressed on myeloid cells 1 (TREM-1) is implicated in multiple inflammatory conditions. In this study, we used potentially novel ligand-independent TREM-1 inhibitors in preclinical models of fibrosis and explanted SSc skin fibroblasts in order to investigate the pathogenic role of TREM-1 in SSc. Selective pharmacological TREM-1 blockade prevented and reversed skin fibrosis induced by bleomycin in mice and mitigated constitutive collagen synthesis and myofibroblast features in SSc fibroblasts in vitro. Our results implicate aberrantly activated TREM-1 signaling in SSc pathogenesis, identify a unique approach to TREM-1 blockade, and suggest a potential therapeutic benefit for TREM-1 inhibition.<\/jats:p>","DOI":"10.1172\/jci.insight.176319","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T12:00:49Z","timestamp":1729166449000},"source":"Crossref","is-referenced-by-count":8,"title":["Inhibiting triggering receptor expressed on myeloid cells 1 signaling to ameliorate skin fibrosis"],"prefix":"10.1172","volume":"9","author":[{"given":"Swarna","family":"Bale","sequence":"first","affiliation":[{"name":"Michigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Verma","sequence":"additional","affiliation":[{"name":"Michigan Scleroderma Program, Division of Rheumatology, Department of 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