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

Author

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  • Benyu Liu

    (Chinese Academy of Sciences)

  • Buqing Ye

    (Chinese Academy of Sciences)

  • Xiaoxiao Zhu

    (Chinese Academy of Sciences)

  • Liuliu Yang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Huimu Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Nian Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Pingping Zhu

    (Chinese Academy of Sciences)

  • Tiankun Lu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Luyun He

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yong Tian

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zusen Fan

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

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.

Suggested Citation

  • Benyu Liu & Buqing Ye & Xiaoxiao Zhu & Liuliu Yang & Huimu Li & Nian Liu & Pingping Zhu & Tiankun Lu & Luyun He & Yong Tian & Zusen Fan, 2020. "An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17944-5
    DOI: 10.1038/s41467-020-17944-5
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    Cited by:

    1. Nian Liu & Jiacheng He & Dongdong Fan & Yang Gu & Jianyi Wang & Huimu Li & Xiaoxiao Zhu & Ying Du & Yong Tian & Benyu Liu & Zusen Fan, 2022. "Circular RNA circTmem241 drives group III innate lymphoid cell differentiation via initiation of Elk3 transcription," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Zhenzhen Chen & Qiankun He & Tiankun Lu & Jiayi Wu & Gaoli Shi & Luyun He & Hong Zong & Benyu Liu & Pingping Zhu, 2023. "mcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming and self-renewal of liver TICs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Wanying Wu & Jinyang Zhang & Xiaofei Cao & Zhengyi Cai & Fangqing Zhao, 2022. "Exploring the cellular landscape of circular RNAs using full-length single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Zhe Gong & Jinjin Zhu & Junxin Chen & Fan Feng & Haitao Zhang & Zheyuan Zhang & Chenxin Song & Kaiyu Liang & Shuhui Yang & Shunwu Fan & Xiangqian Fang & Shuying Shen, 2023. "CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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