Opposing functions of circadian protein DBP and atypical E2F family E2F8 in anti-tumor Th9 cell differentiation

Abstract Interleukin-9 (IL-9)-producing CD4 +T helper cells (Th9) have been implicated in allergy/asthma and anti-tumor immunity, yet molecular insights on their differentiation from activated T cells, driven by IL-4 transforming growth factor-beta (TGF-β), is still lacking. Here we show opposing functions of two transcription factors, D-binding protein (DBP) E2F8, controlling Th9 differentiation. Specifically, TGF-β signaling induces phosphorylation the serine 213 site linker region Smad3 (pSmad3L-Ser 213) via phosphorylated p38, which necessary sufficient for Il9 gene transcription. We identify DBP E2F8 as an activator repressor, respectively, pSmad3L-Ser 213. Notably, with siRNA-mediated knockdown Dbp or E2f8 promote suppress tumor growth, mouse models. Importantly, also exhibit regulating human TH9 vitro. Thus, our data uncover a mechanism region-mediated, Open Access funding provided National Institutes Health (NIH).