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While macrophages are essential mediators of diabetic wound healing, the specific regulatory role that Trem2 plays in this setting remains to be established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study was developed to explore the potential importance of Trem2 signalling in diabetic wound healing and to clarify the underlying mechanisms through which it functions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Following wound induction, diabetic model mice exhibited pronounced upregulation of Trem2 expression, which was primarily evident in macrophages. No cutaneous defects were evident in mice bearing a macrophage\u2010specific knockout of Trem2 (T2\u2010cKO), but they induced more pronounced inflammatory responses and failed to effectively repair cutaneous wounds, with lower levels of neovascularization, slower rates of wound closure, decreased collagen deposition following wounding. Mechanistically, we showed that interleukin (IL)\u20104 binds directly to Trem2, inactivating MAPK\/AP\u20101 signalling to suppress the expression of inflammatory and chemoattractant factors. Co\u2010culture of fibroblasts and macrophages showed that macrophages from T2\u2010cKO mice suppressed the in vitro activation and proliferation of dermal fibroblasts through upregulation of leukaemia inhibitory factor (Lif). Injecting soluble Trem2 in vivo was also sufficient to significantly curtail inflammatory responses and to promote diabetic wound healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These analyses offer novel insight into the role of IL\u20104\/Trem2 signalling as a mediator of myeloid cell\u2010fibroblast crosstalk that may represent a viable therapeutic target for efforts to enhance diabetic wound healing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70026","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T01:20:40Z","timestamp":1727745640000},"source":"Crossref","is-referenced-by-count":17,"title":["Trem2 acts as a non\u2010classical receptor of interleukin\u20104 to promote diabetic wound 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Changzheng Hospital Naval Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxiang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Shanghai General Hospital, School of Medicine Shanghai Jiaotong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Shanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE) Shanghai Changzheng Hospital Naval Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwei","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Dermatology Shanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE) Shanghai Changzheng Hospital Naval Medical 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