NFIL3/E4BP4 controls type 2 T helper cell cytokine expression

Type 2 T helper (T H²) 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 H² cells. NFIL3 is highly expressed in T H² cells but much less in T H 1 cells. Production of interleukin (IL)-13 and IL-5 is significantly increased in Nfil3 ^-/-' T H² cells and is decreased by expression of NFIL3 in wild-type T H² cells. NFIL3 directly binds to and negatively regulates the Il13 gene. In contrast, IL-4 production is decreased in Nfil3 ^-/-' T H² 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 H² cytokine production is a T-cell intrinsic effect. Taken together, these data indicate that NFIL3 is a key regulator of T H² responses.