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Cited by 37interferon and immune responsesMicroRNA in disease regulationImmune Response and Inflammation

miR-23a/b suppress cGAS-mediated innate and autoimmunity

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Yu, Qiuya, Chu, Lei, Li, Yongxing, Wang, Quanyi, Zhu, Juanjuan, Wang, Chen, Cui, Shufang·2021·Cellular & Molecular Immunology
DOI 10.1038/s41423-021-00668-xPMC PMC8093233
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Abstract

Cyclic GMP-AMP synthase (cGAS), a key sensor of intracellular DNA, is essential for eliciting innate immunity against infection, whereas aberrant activation of cGAS by endogenous DNA promotes severe autoimmune diseases. However, it is largely unknown how cGAS expression is regulated during pathogen infection and autoimmunity. Here, we report that during herpes simplex virus type 1 (HSV-1) infection, two microRNAs (miR-23a and miR-23b) whose levels significantly decrease due to their interaction with the lncRNA Oasl2-209 directly regulate the expression of cGAS. Overexpression of miR-23a/b markedly dampens cytosolic DNA-induced innate immune responses, whereas inhibition of miR-23a/b enhances these responses. Mice treated with miR-23a/b agomirs exhibit increased susceptibility to HSV-1 infection. Moreover, cGAS is significantly upregulated in the Trex1−/− mouse autoimmune disease model. Administration of miR-23a/b blunts self DNA-induced autoinflammatory responses in Trex1−/− mice. Collectively, our study not only reveals a novel regulatory mechanism of cGAS expression by miRNAs but also identifies a potential therapy for cGAS-related autoimmune diseases.

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  • The interaction between miR-23a/b and lncRNA Oasl2-209 controls cGAS expression, thereby suppressing cytoplasmic DNA-induced autoinflammatory responses and evoking innate immunity against infection.

    “The interaction between miR-23a/b and lncRNA Oasl2-209 immediately controls the expression of Cyclic GMP-AMP synthase (cGAS), thereby suppressing cytoplasmic DNA-induced autoinflammatory responses and evoking innate immunity against infection [32].”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [32]

    The Results section on Oasl2-209 shows that it binds miR-23a/b and lowers their levels; the Discussion says this raises cGAS expression and boosts antiviral responses. But the Results section on autoimmunity attributes reduced self-DNA-induced inflammation to administering miR-23a/b, not to their interaction with Oasl2-209. The sentence incorrectly combines those effects into one consequence of the interaction. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Overexpression of miR-23a/b via angomirs in mice results in elevated susceptibility to herpes simplex virus type 1 infection.

    “Additionally, the overexpression of miR-23a/b via angomirs in mice results in an elevated susceptibility to herpes simplex virus type 1 (HSV-1) infection.”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [32]

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Research works printed but not linked: 47

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Authors
Yu, Q., Chu, L., Li, Y., Wang, Q., Zhu, J., Wang, C., & Cui, S.
Affiliations
China Pharmaceutical University (CN)
Corresponding author
  • Wang, Chen
  • Cui, Shufang
ORCID
Venue
Cellular & Molecular Immunology
Publisher
Springer Science and Business Media LLC
Published
2021-03-25
Volume
18
Issue
5
Pages
1235-1248
ISSN
  • 1672-7681 (ISSN-L)
  • 2042-0226
DOI
10.1038/s41423-021-00668-x
PMC
PMC8093233
OpenAlex
W3136100821
Cited by
37
References
55
Citations by year
2026: 3 · 2025: 9 · 2024: 11 · 2023: 7 · 2022: 5 · 2021: 2
FWCI
2.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (31801076)
  • China Postdoctoral Science Foundation (2018M630641)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
miR-23a, miR-23b, cGAS, microRNA regulation, herpes simplex virus type 1, innate immunity, autoimmunity, cytosolic DNA sensing, autoinflammatory disease, antiviral immunity
MeSH terms
Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Animals, Base Sequence, Cytosol, DNA, Gene Expression Regulation, Herpes Simplex, Humans, Immunity, Innate, Interferon Type I, Male, Mice, Inbred C57BL, Nucleotidyltransferases, Signal Transduction, Autoimmunity, Herpesvirus 1, Human, MicroRNAs, Mice, HEK293 Cells, RNA, Long Noncoding

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