Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 18, Issue 6, Pages 1412-1424Publisher
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-021-00680-1
Keywords
circZbtb20; ILC3; Alkbh5; Nr4a1; Homeostasis
Categories
Funding
- Ministry of Science and Technology of China [2020YFA0803501, 2019YFA0508501]
- National Natural Science Foundation of China [31930036, 81921003, 92042302, 31870883, 91940305, 31728006, 81772646, 31871494]
- Strategic Priority Research Programs of the Chinese Academy of Sciences [XDB19030203]
- Beijing Natural Science Foundation [5192018]
- Biological Resource Program of the Chinese Academy of Science [KFJ-BRP-017-04]
- Young Elite Scientist Sponsorship Program of CAST [2018QNRC001]
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The newly identified circular RNA circZbtb20 is crucial for the maintenance and function of group 3 innate lymphoid cells (ILC3), with its deletion causing reduced ILC3 numbers and increased susceptibility to bacterial infections. The circZbtb20 enhances the stability of specific mRNA and initiates a signaling pathway to maintain the homeostasis of ILC3.
Group 3 innate lymphoid cells (ILC3s) play critical roles in innate immunity and gut homeostasis. However, how ILC3 homeostasis is regulated remains elusive. Here, we identified a novel circular RNA, circZbtb20, that is highly expressed in ILC3s and required for their maintenance and function. CircZbtb20 deletion causes reduced ILC3 numbers, increasing susceptibility to C. rodentium infection. Mechanistically, circZbtb20 enhances the interaction of Alkbh5 with Nr4a1 mRNA, leading to ablation of the m(6)A modification of Nr4a1 mRNA to promote its stability. Nr4a1 initiates Notch2 signaling activation, which contributes to the maintenance of ILC3 homeostasis. Deletion of Alkbh5 or Nr4a1 also impairs ILC3 homeostasis and increases susceptibilities to bacterial infection. Thus, our findings reveal an important role of circular RNA in the regulation of innate lymphoid cell homeostasis.
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