IL-25 promotes TH2 responses through the induction of IL-2 (47.34)

Abstract

Abstract Dysregulated CD4+ T helper type 2 (TH2) responses are a predominant feature of allergic inflammation, asthma and ulcerative colitis. Unlike TH1 and TH17 cells that employ distinct innate cell-derived cytokines to initiate their differentiation programs (IL-12 for TH1 cells and IL-6 and TGF-β for TH17 cells), TH2 cell development appears to be regulated primarily by autocrine IL-2 and IL-4. However, the factors that regulate expression of IL-2 in developing TH2 cells remain unclear. Here, we demonstrate that the cytokine IL-25 (IL-17E) induces early expression of IL-2 in developing TH2 cells, enhances TH2 cell proliferation and can promote TH2 cell development in the absence of IL-4Rα signaling. Surprisingly, IL-2 was not required for the IL-25-induced increase in CD4+ T cell proliferation, but the ability of IL-25 to promote TH2 responses was lost in the absence of IL-2. In vivo, treatment of resistant mice with an antibody against IL-2 results in impaired TH2 cell-mediated immunity to Trichuris infection. Together, these results identify IL-25 as an upstream differentiation factor for TH2 cells and suggest that manipulation of IL-25 may provide therapeutic benefits for diseases associated with dysregulated TH2 responses.