| Autor: |
Yao Xiang, Jorge Mata-Garrido, Christophe desterke, Eric Batsché, Ahmed Hamaï, Youssouf Sereme, David Skurnik, Abdelali Jalil, Jean-Christophe Beche, Eliane Piaggio, Laurence Arbibe, Yunhua Chang |
| Rok vydání: |
2022 |
| Popis: |
Interferon gamma (IFN-γ) plays central roles in the pathophysiology of inflammatory bowel disease (IBD), both activating inflammatory responses and immunosuppressive functions. However, the epigenetic mechanisms controlling the expression of IFN-γ responsive genes at the gut epithelial barrier are not well understood. In this study, we identified the epigenetic regulator HP1γ as a transcriptional repressor of the IFN-γ-responsive genes STAT1 (signal transducer and activator of transcription 1) and PD-L1 (Programmed Cell Death Ligand 1). Accordingly, HP1γ gene inactivation in the mouse gut epithelium resulted in an immunopathology with a long-lasting up-regulation of STAT1 and PD-L1.Colon organoids models and in vitrocell lines showed that HP1γ deficiency primed STAT1 and PD-L1 expressions, ultimately sensitizing epithelial cells to IFN-γ stimulation. Chromatin immunoprecipitation experiments suggest that HP1 promoter tethering is involved in the silencing of gene expression. Overall, these results identify HP1γ as an epigenetic silencing pathway controlling the IFN-γ response at the epithelial barrier. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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