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The mechanism by which exogenous GM-CSF ameliorates the severity of Crohn\u2019s disease in humans and colitis in murine models has mainly been considered to reflect its activity on myeloid cells. We used GM-CSF\u2013deficient (GM-CSF\u2212\/\u2212) mice to probe the functional role of endogenous host-produced GM-CSF in a colitis model induced after injury to the colon epithelium. Dextran sodium sulfate (DSS), at doses that resulted in little epithelial damage and mucosal ulceration in wild type mice, caused marked colon ulceration and delayed ulcer healing in GM-CSF\u2212\/\u2212 mice. Colon crypt epithelial cell proliferation in vivo was significantly decreased in GM-CSF\u2212\/\u2212 mice at early times after DSS injury. This was paralleled by decreased expression of crypt epithelial cell genes involved in cell cycle, proliferation, and wound healing. Decreased crypt cell proliferation and delayed ulcer healing in GM-CSF\u2212\/\u2212 mice were rescued by exogenous GM-CSF, indicating the lack of a developmental abnormality in the epithelial cell proliferative response in those mice. Nonhematopoietic cells, and not myeloid cells, produced the GM-CSF important for colon epithelial proliferation after DSS-induced injury, as revealed by bone marrow chimera and dendritic cell\u2013depletion experiments, with colon epithelial cells being the cellular source of GM-CSF. Endogenous epithelial cell\u2013produced GM-CSF has a novel nonredundant role in facilitating epithelial cell proliferation and ulcer healing in response to injury of the colon crypt epithelium.<\/jats:p>","DOI":"10.4049\/jimmunol.1202368","type":"journal-article","created":{"date-parts":[[2013,1,17]],"date-time":"2013-01-17T07:28:45Z","timestamp":1358407725000},"page":"1702-1713","source":"Crossref","is-referenced-by-count":74,"title":["GM-CSF Produced by Nonhematopoietic Cells Is Required for Early Epithelial Cell Proliferation and Repair of Injured Colonic Mucosa"],"prefix":"10.1093","volume":"190","author":[{"given":"Laia","family":"Egea","sequence":"first","affiliation":[{"name":"Laboratory of Mucosal Immunology, Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S","family":"McAllister","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Lakhdari","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivelina","family":"Minev","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Shenouda","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin F","family":"Kagnoff","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, Department of Medicine, University of California , San Diego, La Jolla, CA 92093"},{"name":"Department of Pediatrics, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,2,15]]},"reference":[{"key":"2025032406332707800_r1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nri2356","article-title":"Colony-stimulating factors in inflammation and autoimmunity","volume":"8","author":"Hamilton","year":"2008","journal-title":"Nat. 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