NFIL3/E4BP4 controls type 2 T helper cell cytokine expression

Type 2 T helper (T H 2) 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 T H 2 cells. NFIL3 is highly expressed in T H 2 cells but much less in T H 1 cells. Production of interleukin (IL)‐13 and IL‐5 is significantly increased in Nfil3 −/− T H 2 cells and is decreased by expression of NFIL3 in wild‐type T H 2 cells. NFIL3 directly binds to and negatively regulates the Il13 gene. In contrast, IL‐4 production is decreased in Nfil3 −/− T H 2 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 T H 2 cytokine production is a T‐cell intrinsic effect. Taken together, these data indicate that NFIL3 is a key regulator of T H 2 responses.