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Nature Immunology 8, 958–966 (1 September 2007) | doi:10.1038/ni1500

The development of inflammatory TH-17 cells requires interferon-regulatory factor 4

Anne Br|[uuml]|stle , Sylvia Heink , Magdalena Huber , Christine Rosenpl|[auml]|nter , Christine Stadelmann , Philipp Yu , Enrico Arpaia , Tak W Mak , Thomas Kamradt & Michael Lohoff

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|[minus]|/|[minus]|) 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|[minus]|/|[minus]| mice rendered the mice susceptible to experimental autoimmune encephalomyelitis. Irf4|[minus]|/|[minus]| T helper cells had less expression of RORγt 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|[minus]|/|[minus]| 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.