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Recent studies highlight the direct impact of vitamin D receptor (VDR) signaling on intestinal and microbial homeostasis. However, the tissue\u2010specific role of immune VDR signaling is not fully understood. Here, we generated a myeloid\u2010specific VDR knockout (VDR\n                    <jats:sup>\u0394Lyz<\/jats:sup>\n                    ) mouse model and used a macrophage\/enteroids coculture system to examine tissue\u2010specific VDR signaling in intestinal homeostasis. VDR\n                    <jats:sup>\u0394Lyz<\/jats:sup>\n                    mice exhibited small intestine elongation and impaired Paneth cell in maturation and localization. Coculture of enteroids with VDR\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    macrophages increased the delocalization of Paneth cells. VDR\n                    <jats:sup>\u0394Lyz<\/jats:sup>\n                    mice exhibited significant changes in the microbiota taxonomic and functional files, and susceptibility to\n                    <jats:italic>Salmonella<\/jats:italic>\n                    infection. Interestingly, loss of myeloid VDR impaired Wnt secretion in macrophages, thus inhibiting crypt \u03b2\u2010catenin signaling and disrupting Paneth cell differentiation in the epithelium. Taken together, our data have demonstrated that myeloid cells regulate crypt differentiation and the microbiota in a VDR\u2010dependent mechanism. Dysregulation of myeloid VDR led to high risks of colitis\u2010associated diseases. Our study provided insight into the mechanism of immune\/Paneth cell cross talk in regulating intestinal homeostasis.\n                  <\/jats:p>","DOI":"10.1096\/fj.202202169rr","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T10:07:25Z","timestamp":1684836445000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Myeloid vitamin D receptor regulates Paneth cells and microbial homeostasis"],"prefix":"10.1096","volume":"37","author":[{"given":"Danika S.","family":"Bakke","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine University of Illinois Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jilei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine University of Illinois Chicago  Chicago 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