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

Barbara U. Schraml, Kai Hildner, Wataru Ise, Wan Ling Lee, Whitney A.E. Smith, Ben Solomon, Gurmukh Sahota, Julia Sim, Ryuta Mukasa, Saso Cemerski, Robin D. Hatton, Gary D. Stormo, Casey T. Weaver, John H. Russell, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

395 Scopus citations

Abstract

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-producing 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 H 1 and T H 2 differentiation, but show a defect in T H 17 differentiation, and are resistant to experimental autoimmune encephalomyelitis. 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-/- T cells. The Il17 promoter is BATF-responsive, and after T H 17 differentiation, BATF binds conserved intergenic elements in the Il17a-Il17f locus and to the Il17, Il21 and Il22 (ref. 18) promoters. These results demonstrate that the AP-1 protein BATF has a critical role in T H 17 differentiation.

Original languageEnglish
Pages (from-to)405-409
Number of pages5
JournalNature
Volume460
Issue number7253
DOIs
StatePublished - Jul 16 2009

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