{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:45:45Z","timestamp":1791276345286,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2015,4,3]],"date-time":"2015-04-03T00:00:00Z","timestamp":1428019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Accumulating evidence has identified the profibrogenic properties of IL-17A in organ fibrosis. However, the role of IL-17A signal in liver fibrosis induced by Schistosoma japonicum infection remains unclear. In this study, we investigated liver fibrosis in wild-type (WT) and IL-17RA\u2212\/\u2212 mice upon S. japonicum infection. Hepatic IL-17A, IL-17C, IL-17E (IL-25), IL-17F, IL-17RA, IL-17RB and IL-17RC transcript levels were determined by RT-PCR. IL-17A+ cells were analyzed by flow cytometry and confocal microscopy among granuloma cells. Immunostaining of IL-17R was performed on liver sections. Collagen deposition was assessed by Van Gieson\u2019s staining. IL-17A, IL-17C, IL-17E, IL-17F, IL-17RA and IL-17RC mRNA levels were dramatically increased in fibrotic livers. Among granuloma cells, CD3+ and CD3\u2212 lymphocytes, neutrophils and macrophages were found to express IL-17A. Compared to WT, IL-17RA\u2212\/\u2212 mice displayed attenuated granulomatous inflammation, liver fibrosis, improved liver function and high survival. Meanwhile, \u03b1-smooth muscle actin staining and the expression of fibrogenic genes (transforming growth factor \u03b2, IL-13 and collagen-I) as well as IL-17A\u2013induced proinflammatory mediators (IL-1\u03b2, IL-6, tumor necrosis factor \u03b1, CXCL1 and CXCL2) and proteinases (MMP3 and TIMP1) involved in fibrosis were markedly reduced in IL-17RA\u2212\/\u2212 mice. In addition, Th2 cytokines IL-4 and IL-17E (IL-25) were also decreased in IL-17RA\u2212\/\u2212 mice. These results indicated that IL-17A signal contributes to the pathogenesis of liver fibrosis in murine schistosomiasis. This effect was induced possibly by activating hepatic stellate cells and stimulating the release of proinflammatory cytokines and chemokines. Furthermore, the Th2 response was also enhanced by IL-17A signals. Our data demonstrate that IL-17A may serve as a promising target for antifibrotic therapy.<\/jats:p>","DOI":"10.1093\/intimm\/dxv017","type":"journal-article","created":{"date-parts":[[2015,4,4]],"date-time":"2015-04-04T00:12:15Z","timestamp":1428106335000},"page":"317-325","source":"Crossref","is-referenced-by-count":40,"title":["Lack of IL-17 signaling decreases liver fibrosis in murine schistosomiasis japonica"],"prefix":"10.1093","volume":"27","author":[{"given":"Yuxia","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dake","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenda","family":"Gao","sequence":"additional","affiliation":[{"name":"Antagen Institute for Biomedical Research 2 , Boston, MA 02118 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Department 1, Institute of Surgery Research, Daping Hospital, Third Military Medical University 3 , Chongqing 400042 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanling","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiping","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jijia","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Anhui Medical University 1 , Hefei, Anhui 230032 , PR China"},{"name":"Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Medical University 4 , Hefei 230032, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,4,3]]},"reference":[{"key":"2022072019584489000_CIT0001","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.immuni.2004.08.018","article-title":"Interleukin-17 family members and inflammation","volume":"21","author":"Kolls","year":"2004","journal-title":"Immunity"},{"key":"2022072019584489000_CIT0002","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/nri2586","article-title":"Structure and signalling in the IL-17 receptor family","volume":"9","author":"Gaffen","year":"2009","journal-title":"Nat. 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