Lack of IL-17 signaling decreases liver fibrosis in murine schistosomiasis japonica

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 ste...
Source: International Immunology - Category: Allergy & Immunology Authors: Tags: Original Research Source Type: research