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Here, we used a three-dimensional (3D) skin model to study how CD14\n                    <jats:sup>+<\/jats:sup>\n                    monocytes, M1 and M2-like macrophages induce fibroblasts activation and contraction in collagen type I hydrogels. We identified that the co-culture of dermal (myo)fibroblasts with monocytes displayed strong spontaneous hydrogel contraction, coupled with an upregulation of myofibroblast activation-associated markers, such as alpha-smooth muscle actin (\u03b1-SMA). Using transcription factor-responsive reporter constructs and small-molecule inhibitors, we demonstrated that monocytes-(myo)fibroblasts communication was mediated by JAK\/STAT3 and TGF-\u03b2\/Smad2\/3 signaling pathways. Flow cytometry analyses revealed that monocytes, after interacting with (myo)fibroblasts, differentiated into a mixed M1\/M2 polarization phenotype, characterized by CD163, CD206, CD86, and HLA-DR expression. Both M1 and M2-like macrophages promoted significant (myo)fibroblast contraction, which could be mimicked by supernatant transfer. TGF-\u03b2 neutralization but not IL-6 blocking abolished this effect. This study demonstrates that monocytes\/macrophages can strongly induce (myo)fibroblasts activation\/contraction. Together, our work contributes to elucidating pathways and mechanisms associated with skin fibrosis in SSc and paves the way for developing new platforms for targeted therapy testing.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-62996-0","type":"journal-article","created":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:54:14Z","timestamp":1784422454000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Monocytes strongly induce (myo)fibroblast contraction in a 3D skin model to understand inflammation-fibrosis crosstalk"],"prefix":"10.1038","volume":"16","author":[{"given":"D. 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