The AP-1 transcription factor Batf controls T_H17 differentiation

摘要

Activator protein 1 (AP-1, also known as JUN) transcription factors are dimers of JUN, FOS, MAF and activating transcription factor (ATF) family proteins characterized by basic region and leucine zipper domains. Many AP-1 proteins contain defined transcriptional activation domains, but BATF and the closely related BATF3 (refs 2, 3) contain only a basic region and leucine zipper, and are considered to be inhibitors of AP-1 activity. Here we show that Batf is required for the differentiation of IL17-pro-ducing T helper (T_H 17) cells. T_H 17 cells comprise a CD4~+ T-cell subset that coordinates inflammatory responses in host defence but is pathogenic in autoimmunity. Batf~(-/-) mice have normal T_H1 and T_H2 differentiation, but show a defect in T_H17 differentiation, and are resistant to experimental autoimmune encephalo-myelitis. Batf~(-/-) T cells fail to induce known factors required for T_H 17 differentiation, such as RORγt (encoded by Rorc) and the cytokine IL21 (refs 14-17). Neither the addition of IL21 nor the overexpression of RORγt fully restores IL17 production in Batf~(-1-) T cells. The Il17 promoter is BATF-responsive, and after T_H17 differentiation, BATF binds conserved intergenic elements in the Il17a-Il17 flocus and to the Il17,I121 and Il122 (ref. 18) promoters. These results demonstrate that the AP-1 protein BATF has a critical role in T_H17 differentiation.