RTF1 mediates epigenetic control of Th17 cell differentiation via H2B monoubiquitination 2393

Abstract Description A gene encoding the transcription factor RTF1 has been associated with an increased risk of ulcerative colitis (UC). In this study, we investigated its function in modulating T cells expressing interleukin-17A (Th17 cells), a cardinal cell type promoting intestinal inflammation. Our results indicate that Rtf1 deficiency disrupts the differentiation of Th17 cells, while leaving regulatory T cells (Treg) unaffected. Mechanistically, RTF1 facilitates histone H2B monoubiquitination (H2Bub1), which requires its histone modification domain (HMD), for supporting Th17 cell function. Impaired Th17 differentiation was also observed in cells lacking the H2Bub1 E3 ligase subunit RNF40, an enzyme known to physically interact with RTF1. Thus, our study underscores the essential role of RTF1 in H2Bub1-mediated epigenetic regulation of Th17 cell differentiation. Understanding this process will likely provide valuable insights into addressing Th17-associated inflammatory disorders. Funding Sources This study was supported by the NIH grants (R01 DK106351 and R01 DK110559-08) to J.R.H. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)