Novel function of IL-17E in the autoimmune pathogenesis of experimental Sjogren´s syndrome

Abstract

IL-17 family has been implicated in the autoimmune pathogenesis. Our previous study has demonstrated an essential role of IL-17A in the development of primary Sjogren's syndrome (pSS), an autoimmune disorder characterized by tissue destruction in salivary glands. However, the role of IL-17E in the pSS pathogenesis remained unclear. Recently, we have established a mouse model of experimental Sjogren's syndrome (ESS) that highly recapitulates human pSS. In this study, we first detected significantly enhanced IL-17E signature in the salivary tissues of ESS mice. IL-17RB, the receptor of IL-17E was also found increased in the glandular-infiltrating cells. Moreover, we found elevated serum levels of IL-5 and IL-13, increased type 2 innate lymphoid cells (ILC2) and IL-17RB+CD4+ T cells with enhanced expression of TRAF6, the downstream signaling upon IL-17RB activation during ESS development. Interestingly, serum levels of IL-25 was found elevated at the disease chronic stages of ESS mice. Consistently, marked increase of IL-25-producing cells was also detected in the salivary gland of ESS mice with severe lymphocytic infiltrations. To further determine the therapeutic potential of targeting IL-17E, we performed anti-IL-17E neutralization using ESS mice at disease chronic stages. Notably, anti-IL-17E treatment resulted in clinical improvement in diseased mice, including ameliorated salivary histopathology and significantly decreased glandular-infiltrating cells, including ILC2 and Th1 cells when compared with those mice treated with vehicles, suggesting that IL-17E may serve as promising candidate in the treatment of human pSS.