An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution

• Published in: Nature communications Vol. 11; no. 1; p. 4076
• Main Authors: Liu, Benyu, Ye, Buqing, Zhu, Xiaoxiao, Yang, Liuliu, Li, Huimu, Liu, Nian, Zhu, Pingping, Lu, Tiankun, He, Luyun, Tian, Yong, Fan, Zusen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14-08-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 38/15; 38/61; 631/250/2502; 631/250/2504/2506; 631/250/256; 631/337/384; Activation; Circular RNA; Circularity; Colitis; Deactivation; Deletion; Dextran; Dextrans; Digestive system; Gastrointestinal tract; Homeostasis; Humanities and Social Sciences; Immunity; Inactivation; Inflammation; Inflammatory bowel disease; Interleukin 1; Interleukin 17; Intestine; Lymphoid cells; MBD3 protein; multidisciplinary; RAG1 protein; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Sodium sulfate
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-17944-5

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
−/−
Rag1
−/−
and
circKcnt2
−/−
Rag1
−/−
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.
Type 3 innate lymphoid cells (ILC3) are involved in maintaining gut immune homeostasis. Here the authors identify a circular RNA,
circKcnt2
, to be induced in ILC3s from inflamed gut, yet
circKcnt2
deletion aggravates mouse experimental colitis, thereby implicating
circKcnt2
as a potential feedback regulator of ILC3 activation and gut immunity.