Immune translational control by CPEB4 regulates intestinal inflammation resolution and colorectal cancer development

• Published in: iScience 2022-02, Vol.25 (2), p.103790-103790, Article 103790
• Main Authors: Sibilio, Annarita, Suñer, Clara, Fernández-Alfara, Marcos, Martín, Judit, Berenguer, Antonio, Calon, Alexandre, Chanes, Veronica, Millanes-Romero, Alba, Fernández-Miranda, Gonzalo, Batlle, Eduard, Fernández, Mercedes, Méndez, Raúl
• Format: Article
• Language: English
• Subjects: Biological sciences; Immunology; Molecular biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.103790

Upon tissue injury, cytokine expression reprogramming transiently remodels the inflammatory immune microenvironment to activate repair processes and subsequently return to homeostasis. However, chronic inflammation induces permanent changes in cytokine production which exacerbate tissue damage and may even favor tumor development. Here, we address the contribution of post-transcriptional regulation, by the RNA-binding protein CPEB4, to intestinal immune homeostasis and its role in inflammatory bowel diseases (IBD) and colorectal cancer (CRC) development. We found that intestinal damage induces CPEB4 expression in adaptive and innate immune cells, which is required for the translation of cytokine mRNA(s) such as the one encoding interleukin-22. Accordingly, CPEB4 is required for the development of gut-associated lymphoid tissues and to maintain intestinal immune homeostasis, mediating repair and remodeling after acute inflammatory tissue damage and promoting the resolution of intestinal inflammation. CPEB4 is chronically overexpressed in inflammatory cells in patients with IBD and in CRC, favoring tumor development. [Display omitted] •CPEB4 is overexpressed in Th17 and ILC3 cells upon intestinal barrier damage•CPEB4 is required for Il-22 mRNA translation and IL-22 expression•CPEB4 promotes tissue repair in acute transient inflammation•In chronic inflammation CPEB4 exacerbates intestinal pathology and promotes tumor growth Biological sciences; Molecular biology; Immunology