1. The AP-1 transcription factor Batf controls [T.sub.H]17 differentiation
- Author
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Schraml, Barbara U., Hildner, Kai, Ise, Wataru, Lee, Wan-Ling, Smith, Whitney A.-E., Solomon, Ben, Sahota, Gurmukh, Sim, Julia, Mukasa, Ryuta, Cemerski, Saso, Hatton, Robin D., Stormo, Gary D., Weaver, Casey T., Russell, John H., Murphy, Theresa L., and Murphy, Kenneth M.
- Subjects
Immunohistochemistry -- Usage -- Methods -- Physiological aspects -- Research ,Gene expression -- Research -- Physiological aspects -- Methods -- Genetic aspects -- Usage ,T cells -- Physiological aspects -- Genetic aspects -- Research -- Methods -- Usage ,DNA binding proteins -- Physiological aspects -- Genetic aspects -- Research -- Usage -- Methods ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - 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 (1). 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 (3-8). Here we show that Batf is required for the differentiation of IL17-producing T helper ([T.sub.H]17) cells (9). [T.sub.H]17 cells comprise a [CD4.sup.+] T-cell subset that coordinates inflammatory responses in host defence but is pathogenic in autoimmunity (10-13). [Batf.sup.-/-] mice have normal [T.sub.H]1 and [T.sub.H]2 differentiation, but show a defect in [T.sub.H]17 differentiation, and are resistant to experimental autoimmune encephalomyelitis. [Batf.sup.-/-] T cells fail to induce known factors required for [T.sub.H]17 differentiation, such as RORγt (11) (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.sup.-/-] T cells. The Il17 promoter is BATF-responsive, and after [T.sub.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.sub.H]17 differentiation., In a gene expression survey (Supplementary Fig. la), we identified the basic leucine zipper transcription factor ATF-like (7) Batf to be highly expressed in [T.sub.H]1, [T.sub.H]2 and [T.sub.H]17 cells compared [...]
- Published
- 2009