The AP-1 transcription factor Batf controls TH17 differentiation

By Barbara U. Schraml, K. Hildner, W. Ise, Wan-Ling Lee, W. Smith, Ben Solomon, Gurmukh Sahota, Julia Sim, R. Mukasa, S. Cemerski and 6 more. Nature, 2009

639 citations recorded by the source corpus.

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 (TH17) cells. TH17 cells comprise a CD4+ T-cell subset that coordinates inflammatory responses in host defence but is pathogenic in autoimmunity. Batf-/- mice have normal TH1 and TH2 differentiation, but show a defect in TH17 differentiation, and are resistant to experimental autoimmune encephalomyelitis. Batf-/- T cells fail to induce known factors required for TH17 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 TH17 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 TH17 differentiation.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/4324f6aeecd0e9bfa529771a53cbf6098f37d2eb

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In Immunology

1. Jinfang Zhu
2. W. E. Paul
3. J. O’Shea
4. Y. Kanno
5. A. Laurence
6. F. Powrie
7. Shane Crotty

Citations in the corpus

• CD4+T Cells: Differentiation and Functions (2012, background): “Batf(−/−) mice had defective Th17 response, but Th1 and Th2 development was unaffected [74].”
• Peripheral CD4 T cell differentiation regulated by networks of cytokines and transcription factors (2010, background): “BATF, which is a critical AP-1 factor for RORct induction and IL-17 production, directly binds to the CNS3 site of the Il17a ⁄ Il17f locus, approximately 10 Kb downstream of the Il17a transcription start site (81).”
• Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis (2010, background): “Th17 cell differentiation is associated with expression of several transcription factors, including RORgt, RORa, RUNX1, BATF, IRF-4, AHR, and c-Maf (Bauquet et al., 2009; Brüstle et al., 2007; Ivanov et al., 2006; Schraml et al., 2009; Veldhoen et al., 2008; Yang et al., 2008b; Zhang et al., 2008).”
• Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. (2011, neutral): “, 2008), BATF (Schraml et al., 2009), Stat3, c-Maf (Bauquet et al.”