An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32796851.
- Also identified by DOI 10.1038/s41467-020-17944-5 and PMC identifier 7427797.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Group 3 innate lymphoid cells (ILC3) are an important regulator for immunity, inflammation and tissue homeostasis in the intestine, but how ILC3 activation is regulated remains elusive. Here we identify a new circular RNA (circRNA) circKcnt2 that is induced in ILC3s during intestinal inflammation. Deletion of circKcnt2 causes gut ILC3 activation and severe colitis in mice. Mechanistically, circKcnt2, as a nuclear circRNA, recruits the nucleosome remodeling deacetylase (NuRD) complex onto Batf promoter to inhibit Batf expression; this in turn suppresses Il17 expression and thereby ILC3 inactivation to promote innate colitis resolution. Furthermore, Mbd3<sup>-/-</sup>Rag1<sup>-/-</sup> and circKcnt2<sup>-/-</sup>Rag1<sup>-/-</sup> mice develop severe innate colitis following dextran sodium sulfate (DSS) treatments, while simultaneous deletion of Batf promotes colitis resolution. In summary, our data support a function of the circRNA circKcnt2 in regulating ILC3 inactivation and resolution of innate colitis.
Medical subject headings
- Colitis
- Lymphocytes
- Potassium Channels, Sodium-Activated
- RNA, Circular