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)circKcnt2that is induced in ILC3s during intestinal inflammation. Deletion ofcircKcnt2causes gut ILC3 activation and severe colitis in mice. Mechanistically,circKcnt2, as a nuclear circRNA, recruits the nucleosome remodeling deacetylase (NuRD) complex ontoBatfpromoter to inhibit Batf expression; this in turn suppressesIl17expression and thereby ILC3 inactivation to promote innate colitis resolution. Furthermore,Mbd3-/-Rag1-/-andcircKcnt2-/-Rag1-/-mice develop severe innate colitis following dextran sodium sulfate (DSS) treatments, while simultaneous deletion ofBatfpromotes colitis resolution. In summary, our data support a function of the circRNAcircKcnt2in regulating ILC3 inactivation and resolution of innate colitis.
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An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution,Nat Commun, 14 Aug 2020
Nature Communications, 14 August, 2020, DOI：https://doi.org/10.1038/s41467-020-17944-5
An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution
Benyu Liu, Buqing Ye, Xiaoxiao Zhu, Liuliu Yang, Huimu Li, Nian Liu, Pingping Zhu, Tiankun Lu, Luyun He, Yong Tian & Zusen Fan
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)circKcnt2that is induced in ILC3s during intestinal inflammation. Deletion ofcircKcnt2causes gut ILC3 activation and severe colitis in mice. Mechanistically,circKcnt2, as a nuclear circRNA, recruits the nucleosome remodeling deacetylase (NuRD) complex ontoBatfpromoter to inhibit Batf expression; this in turn suppressesIl17expression and thereby ILC3 inactivation to promote innate colitis resolution. Furthermore,Mbd3-/-Rag1-/-andcircKcnt2-/-Rag1-/-mice develop severe innate colitis following dextran sodium sulfate (DSS) treatments, while simultaneous deletion ofBatfpromotes colitis resolution. In summary, our data support a function of the circRNAcircKcnt2in regulating ILC3 inactivation and resolution of innate colitis.
文章链接：https://www.nature.com/articles/s41467-020-17944-5