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It is characterized by the shortening and thickening of the palmar fascia into myofibroblastic nodules that can progress to palmar\u2010digital contractures and permanent loss of dexterity. Molecular analyses of DD tissues and the presence of inflammatory cell infiltrates suggest a pathogenesis initiated by a proinflammatory fascial milieu that promotes myofibroblast activation and palmar fascia contractures. However, the relative contributions of vascular and\/or tissue derived immune system cells and cytokine\u2010sensitive stromal myofibroblasts to the development of this proinflammatory microenvironment are poorly understood. To gain insights into this process, we have developed and tested a collagen\u2010based 3D tissue biomimetic co\u2010culture system to assess paracrine interactions between THP\u20101\u2010derived pro\u2010inflammatory macrophages and primary human palmar fascia myofibroblasts (PFMs). We observed significant and reproducible impacts of collagen\u2010adherent macrophage and PFM co\u2010cultures on the cytokine gene expression profiles of these cells compared to their respective monocultures, and significant changes to the resulting cytokine milieu in their shared culture media, notably TNF and IL\u20106. Our findings are consistent with central roles for PFMs in cytokine production and immunoregulation of the pro\u2010inflammatory milieu hypothesized to promote DD development.<\/jats:p>","DOI":"10.1111\/wrr.12928","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T08:12:07Z","timestamp":1620547927000},"page":"627-636","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Biomimetic analyses of interactions between macrophages and palmar fascia myofibroblasts derived from Dupuytren's disease reveal distinct inflammatory cytokine responses"],"prefix":"10.1111","volume":"29","author":[{"given":"Brianna C.","family":"Gonga\u2010Cav\u00e9","sequence":"first","affiliation":[{"name":"Department of Biochemistry University of Western Ontario  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Maria","family":"Pena Diaz","sequence":"additional","affiliation":[{"name":"Roth McFarlane Hand and Upper Limb Centre Lawson Health Research Institute  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6195-2644","authenticated-orcid":false,"given":"David B.","family":"O'Gorman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Western Ontario  London Ontario Canada"},{"name":"Department of Surgery University of Western Ontario  London Ontario Canada"},{"name":"Roth McFarlane Hand and Upper Limb Centre Lawson Health Research Institute  London Ontario 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