NFIL3/E4BP4 controls type 2 T helper cell cytokine expression

Publisher Website
Google Scholar
Abstract
Type 2 T helper (TH2) cells are critical for the development of allergic immune responses; however, the molecular mechanism controlling their effector function is still largely unclear. Here, we report that the transcription factor NFIL3/E4BP4 regulates cytokine production and effector function by TH2 cells. NFIL3 is highly expressed in TH2 cells but much less in TH1 cells. Production of interleukin (IL)‐13 and IL‐5 is significantly increased in Nfil3 −/− TH2 cells and is decreased by expression of NFIL3 in wild‐type TH2 cells. NFIL3 directly binds to and negatively regulates the Il13 gene. In contrast, IL‐4 production is decreased in Nfil3 −/− TH2 cells. Increased IL‐13 and IL‐5 together with decreased IL‐4 production by antigen‐stimulated splenocytes from the immunized Nfil3 −/− mice was also observed. The ability of NFIL3 to alter TH2 cytokine production is a T‐cell intrinsic effect. Taken together, these data indicate that NFIL3 is a key regulator of TH2 responses.