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IL-17A, a cytokine produced by a variety of cells in response to inflammatory cytokines released following tissue injury, has been implicated in IR injury. Using Il17a\u2212\/\u2212, Il23r\u2212\/\u2212, and Rorc\u2212\/\u2212 mice and administration of anti\u2013IL-17A and anti\u2013IL-23 neutralizing Abs to wild-type mice, we demonstrate that intestinal IR injury depends on IL-17A and that IL-17A is downstream of the binding of autoantibody to ischemia-conditioned tissues and subsequent complement activation. Using bone marrow chimeras, we demonstrate that the IL-17A required for intestinal IR injury is derived from hematopoietic cells. Finally, by transferring autoantibody-rich sera into Rag2\u03b3c\u2212\/\u2212 and Rag2\u2212\/\u2212 mice, we demonstrate that innate lymphoid cells are the main producers of IL-17A in intestinal IR injury. We propose that local production of IL-17A by innate lymphoid cells is crucial for the development of intestinal IR injury and may provide a therapeutic target for clinical exploitation.<\/jats:p>","DOI":"10.4049\/jimmunol.1700655","type":"journal-article","created":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T23:14:36Z","timestamp":1504739676000},"page":"2921-2929","source":"Crossref","is-referenced-by-count":18,"title":["IL-17A Produced by Innate Lymphoid Cells Is Essential for Intestinal Ischemia-Reperfusion Injury"],"prefix":"10.1093","volume":"199","author":[{"given":"Mayya","family":"Geha","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02114"},{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8072-1358","authenticated-orcid":false,"given":"Maria G","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5463-9617","authenticated-orcid":false,"given":"Robin E","family":"Bosse","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3749-576X","authenticated-orcid":false,"given":"Tatyana","family":"Sannikova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Boston Children\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[{"name":"Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science , Chiba 278-0022,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-0999","authenticated-orcid":false,"given":"Jurandir J","family":"Dalle Lucca","sequence":"additional","affiliation":[{"name":"Translational Medical Division, Department of Chemical and Biological Technologies, Defense Threat Reduction Agency , Fort Belvoir, VA 22060"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"De Waal Malefyt","sequence":"additional","affiliation":[{"name":"Merck Sharp & Dohme Corp. , Palo Alto, CA 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9589-2360","authenticated-orcid":false,"given":"George C","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,10,15]]},"reference":[{"key":"2025030614490289900_r1","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/j.1445-2197.1998.tb02099.x","article-title":"Ischaemia-reperfusion injury to the intestine","volume":"68","author":"Kong","year":"1998","journal-title":"Aust. 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