An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution
An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution
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诱导型环状 RNA circKcnt2 抑制 ILC3 激活以促进结肠炎消退
DOI：
10.1038/s41467-020-17944-5
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发表时间：
2020-08-14
影响因子：
16.6
通讯作者：
Fan, Zusen
中科院分区：
文献类型：
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作者：
Liu, Benyu;Ye, Buqing;Fan, Zusen
第3组先天性淋巴样细胞（ILC 3）是肠道免疫、炎症和组织稳态的重要调节因子，但ILC 3的激活如何调节仍然是一个谜。在这里，我们确定了一个新的环状RNA（circRNA）circKcnt 2，在肠道炎症过程中诱导ILC 3。circKcnt 2的缺失导致小鼠肠道ILC 3激活和严重结肠炎。在机制上，circKcnt 2作为核circRNA，将核小体重塑脱乙酰酶（NuRD）复合物募集到Batf启动子上以抑制Batf表达;这进而抑制Il 17表达，从而抑制ILC 3失活以促进先天性结肠炎消退。此外，Mbd 3（-/-）Rag 1（-/-）和circKcnt 2（-/-）Rag 1（-/-）小鼠在葡聚糖硫酸钠（DSS）治疗后发生严重的先天性结肠炎，而同时缺失Batf促进结肠炎消退。总之，我们的数据支持circRNA circKcnt 2在调节ILC 3失活和先天性结肠炎消退中的功能。3型先天淋巴样细胞（ILC 3）参与维持肠道免疫稳态。在这里，作者确定了一种环状RNA，circKcnt 2，在炎症肠道的ILC 3中诱导，但circKcnt 2缺失会导致小鼠实验性结肠炎，从而暗示circKcnt 2是ILC 3激活和肠道免疫的潜在反馈调节因子。
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.