An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution
| Autor: | Nian Liu, Pingping Zhu, Yong Tian, Liuliu Yang, Zusen Fan, Buqing Ye, L.L. He, H.B. Li, Benyu Liu, Tiankun Lu, Xiaoxiao Zhu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
RNA Untranslated General Physics and Astronomy 02 engineering and technology Potassium Channels Sodium-Activated Non-coding RNAs Mice BATF Homeostasis Lymphocytes lcsh:Science Tissue homeostasis Mice Knockout Mice Inbred ICR Multidisciplinary Chemistry Innate lymphoid cell digestive oral and skin physiology Colitis 021001 nanoscience & nanotechnology Cell biology DNA-Binding Proteins Intestines Female medicine.symptom 0210 nano-technology Science Innate lymphoid cells Inflammation digestive system Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Circular RNA Immunity medicine Animals Humans Homeodomain Proteins RNA RNA Circular General Chemistry medicine.disease Immunity Innate Mice Inbred C57BL Disease Models Animal Gene regulation in immune cells 030104 developmental biology lcsh:Q Transcription Factors |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-17944-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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