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

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. D...

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Detalles Bibliográficos
Autores principales: Liu, Benyu, Ye, Buqing, Zhu, Xiaoxiao, Yang, Liuliu, Li, Huimu, Liu, Nian, Zhu, Pingping, Lu, Tiankun, He, Luyun, Tian, Yong, Fan, Zusen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427797/
https://www.ncbi.nlm.nih.gov/pubmed/32796851
http://dx.doi.org/10.1038/s41467-020-17944-5
Descripción
Sumario: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.