title: Lack of IL-17 signaling decreases liver fibrosis in murine schistosomiasis japonica.
abstract: 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(-/-) 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's 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(-) lymphocytes, neutrophils and macrophages were found to express IL-17A. Compared to WT, IL-17RA(-/-) mice displayed attenuated granulomatous inflammation, liver fibrosis, improved liver function and high survival. Meanwhile, α-smooth muscle actin staining and the expression of fibrogenic genes (transforming growth factor β, IL-13 and collagen-I) as well as IL-17A-induced proinflammatory mediators (IL-1β, IL-6, tumor necrosis factor α, CXCL1 and CXCL2) and proteinases (MMP3 and TIMP1) involved in fibrosis were markedly reduced in IL-17RA(-/-) mice. In addition, Th2 cytokines IL-4 and IL-17E (IL-25) were also decreased in IL-17RA(-/-) 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.
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Dake
authors.initials: D
authors.lastname: Huang
authors.affiliation: Antagen Institute for Biomedical Research, Boston, MA 02118, USA.
authors.forename: Wenda
authors.initials: W
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Department 1, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Wanling
authors.initials: W
authors.lastname: Zhou
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hou
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Ren
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Siying
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, PR China Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei 230032, PR China shenjijia@hotmail.com.
authors.forename: Jijia
authors.initials: J
authors.lastname: Shen
mesh_terms: D000818:Animals; D005260:Female; D020381:Interleukin-17 / Q000172:deficiency / Q000276:immunology*; D008103:Liver Cirrhosis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012554:Schistosomiasis japonica / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D020381:Interleukin-17
keywords: IL-17; Schistosoma japonicum; fibrosis; granulomatous inflammation