IL-33 attenuates renal fibrosis via group2 innate lymphoid cells.

Renal fibrosis is a common pathway in the progression of various kidney diseases and injuries. Unilateral ureteral obstruction (UUO) induces renal fibrosis, and immune responses profoundly affect its pathogenesis. Group2 innate lymphoid cells (ILC2s) are strongly activated by interleukin (IL) -33, which is a member of IL-1 family and recognize as alarmin. ILC2s quickly produce large amounts of type 2 cytokines including IL-5 and IL-13, which are involved in inflammation, tissue homeostasis, and wound healing. However, the relationship between renal fibrosis and ILC2s has been unclear. In the present study, we investigated the roles of the ILC2/L-33 axis in renal fibrosis using a UUO model. We found that kidney ILC2s decreased in UUO-affected kidneys compared with their counterpart kidneys despite IL-33 upregulation. There was no effect of reactive oxygen species or TGF-β from reduced ILC2 caused by UUO. Pretreatment with IL-33 before UUO induced ILC2s and Tregs in kidneys and alleviated renal fibrosis. Furthermore, this protective effect was maintained even when CD4T cells was depleted. These findings demonstrated that ILC2s play a predominant role in the suppressive function of renal fibrosis mediated by pretreatment with IL-33. In contrast, post-treatment with IL-33 after UUO increased ILC2s in kidneys but had no therapeutic effect on renal fibrosis. Our findings suggest that ILC2s have potential roles in the prevention of renal fibrosis and can serve as a therapeutic and diagnostic target.