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

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 RORgamma t (encoded by Rorc) and the cytokine IL21 (refs 14-17). Neither the addition of IL21 nor the overexpression of RORgamma t 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.

Pubmed ID: 19578362

Authors

  • Schraml BU
  • Hildner K
  • Ise W
  • Lee WL
  • Smith WA
  • Solomon B
  • Sahota G
  • Sim J
  • Mukasa R
  • Cemerski S
  • Hatton RD
  • Stormo GD
  • Weaver CT
  • Russell JH
  • Murphy TL
  • Murphy KM

Journal

Nature

Publication Data

July 16, 2009

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI035783
  • Agency: NIAMS NIH HHS, Id: AR049293
  • Agency: NIGMS NIH HHS, Id: GM07200
  • Agency: NHGRI NIH HHS, Id: HG00249
  • Agency: NHGRI NIH HHS, Id: R01 HG000249
  • Agency: NHGRI NIH HHS, Id: R01 HG000249-20
  • Agency: NIGMS NIH HHS, Id: T32 GM008802
  • Agency: NIGMS NIH HHS, Id: T32 GM008802-08
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors
  • Cell Differentiation
  • Encephalomyelitis, Autoimmune, Experimental
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Interleukin-17
  • Interleukins
  • Lymph Nodes
  • Male
  • Mice
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Promoter Regions, Genetic
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • T-Lymphocytes, Helper-Inducer
  • Transcription Factor AP-1