The AP-1 transcription factor Batf controls TH17 differentiation

Abstract

Activator protein 1 (AP-1) transcription factors are dimers of Jun, Fos, MAF and activating transcription factor (ATF) family proteins characterized by basic region and leucine zipper domains1. Many AP-1 proteins contain defined transcriptional activation domains (TADs), but Batf and the closely related Batf3 (refs 2, 3) contain only a basic region and leucine zipper and have been considered inhibitors of AP-1 activity3–8. Here we show that Batf is required for the differentiation of IL-17-producing T helper (TH17) cells9. TH17 cells comprise a CD4+ T cell subset that coordinates inflammatory responses in host defense but is pathogenic in autoimmunity10–13.Batf −/−mice have normal TH1 and TH2 differentiation, but show a defect in TH17 differentiation, and are resistant to experimental autoimmune encephalomyelitis (EAE).Batf −/−T cells fail to induce known factors required for TH17 differentiation, such as RORγt11 and the cytokine IL-21 (refs 14–17). Neither addition of IL-21 nor overexpression of RORγt fully restores IL-17 production in Batf−/− T cells. The IL-17 promoter is Batf-responsive, and upon TH17 differentiation, Batf binds conserved intergenic elements in the IL-17A/F locus and to the IL-17, IL-21 and IL-22 (ref 18) promoters. These results demonstrate that the AP-1 protein Batf plays a critical role in TH17 differentiation.

Basic leucine zipper transcription factor, ATF-like (BATF) regulates epigenetically and energetically effector CD8 T-cell differentiation via Sirt1 expression

“…S1C). Consistent with previous reports (10,11), Batf gfp/gfp mice demonstrated a slight increase in splenic B-cell numbers ( Fig. S1 D and E).…”

“…Unlike other AP-1 family members, BATF expression is restricted to lymphoid organs, and is induced in T cells and natural killer T cells upon stimulation. Although BATF-deficient mice show impaired Th17 and follicular Th differentiation and antibody (Ab) production (10,11), the function of BATF in CD8 T-cell differentiation is unknown.…”

Inhibition of AP-1 by SARI negatively regulates transformation progression mediated by CCN1

“…Although there are certain similarities between these two BATF proteins relative to their bZIP domains, sequence alignment indicates only an B26% identity. Therefore, further studies are required to determine whether these two proteins share similar functions, including profound cancer-specific antitumor activity (SARI) or effects on T H 17 differentiation and maturation and expansion of immature NKT cells in the thymus (BATF) (Zullo et al, 2007;Schraml et al, 2009). This paper explains an important link between SARI and CCN1 expression.…”

STAT5 Protein Negatively Regulates T Follicular Helper (Tfh) Cell Generation and Function

“…The following primer pair for c-Maf was used: forward, GCAGAGACACGTCCTGGAG-TCG, and reverse, CGAGCTTGGCCCTGCAACTAGC. The primers for IL-21, CXCR5, Bcl6, Batf, c-Maf, Blimp-1, and ␤-actin were previously described (8,18).…”