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−/−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.
Highlights
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
We recently demonstrated that circPan[3] can promote the self-renewal of intestinal stem cells through IL-13 produced by niche ILC2s18,23
ILC3s are an important regulator for immunity, inflammation, and tissue homeostasis in the intestine[34]
Summary
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. Our data support a function of the circRNA circKcnt[2] in regulating ILC3 inactivation and resolution of innate colitis. 1234567890():,; Innate lymphoid cells (ILCs) mainly reside in mucosal surfaces and play a critical role in sustaining mucosal integrity and promoting lymphoid organogenesis[1,2] According to their specific fate-decision transcription factors (TFs) and secreted cytokines, ILCs can be classified into three subgroups, including group 1 ILC (ILC1s), group 2 ILC (ILC2s), and group 3 ILC (ILC3s)[1,3]. CircKcnt[2] recruits the NuRD complex onto Batf promoter to suppress its expression, which inhibits ILC3 activation to promote innate colitis resolution. These results discover a previously unidentified contribution of circRNA to the regulation of colitis
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