The AP-1 transcription factor Batf controls T(H)17 differentiation

Activator protein 1 (AP-1) transcription factors are dimers of Jun, Fos, MAF and activating transcription factor (ATF) family proteins characterized by basic region and leucine zipper domains1. Many AP-1 proteins contain defined transcriptional activation domains (TADs), but Batf and the closely related Batf3 (refs 2, 3) contain only a basic region and leucine zipper and have been considered inhibitors of AP-1 activity3–8. Here we show that Batf is required for the differentiation of IL-17-producing T helper (T(H)17) cells9. T(H)17 cells comprise a CD4(+) T cell subset that coordinates inflammatory responses in host defense but is pathogenic in autoimmunity10–13.Batf (−/−)mice have normal T(H)1 and T(H)2 differentiation, but show a defect in T(H)17 differentiation, and are resistant to experimental autoimmune encephalomyelitis (EAE).Batf (−/−)T cells fail to induce known factors required for T(H)17 differentiation, such as RORγt11 and the cytokine IL-21 (refs 14–17). Neither addition of IL-21 nor overexpression of RORγt fully restores IL-17 production in Batf(−/−) T cells. The IL-17 promoter is Batf-responsive, and upon T(H)17 differentiation, Batf binds conserved intergenic elements in the IL-17A/F locus and to the IL-17, IL-21 and IL-22 (ref 18) promoters. These results demonstrate that the AP-1 protein Batf plays a critical role in T(H)17 differentiation.