The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4

Abstract

Interferon-regulatory factor 4 (IRF4) is essential for the development of T helper type 2 cells. Here we show that IRF4 is also critical for the generation of interleukin 17–producing T helper cells (TH-17 cells), which are associated with experimental autoimmune encephalomyelitis. IRF4-deficient (Irf4–/–) mice did not develop experimental autoimmune encephalomyelitis, and T helper cells from such mice failed to differentiate into TH-17 cells. Transfer of wild-type T helper cells into Irf4–/– mice rendered the mice susceptible to experimental autoimmune encephalomyelitis. Irf4–/– T helper cells had less expression of RORct and more expression of Foxp3, transcription factors important for the differentiation of TH-17 and regulatory T cells, respectively. Altered regulation of both transcription factors contributed to the phenotype of Irf4–/– T helper cells. Our data position IRF4 at the center of T helper cell development, influencing not only T helper type 2 but also TH-17 differentiation.