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Type I IFN–InducibleDownregulation ofMicroRNA-27a FeedbackInhibits AntiviralInnate Response byUpregulatingSiglec1/TRIM27 Qingliang ZhengJin HouYe Zhou2015 год

Type I IFN–Inducible Downregulation of MicroRNA-27a Feedback Inhibits Antiviral Innate Response by Upregulating Siglec1/TRIM27
статья из журнала

Страница публикацииПубликация в OpenAlex
Аннотация: Abstract Upon recognition of viral components by pattern recognition receptors, including TLRs and retinoic acid–inducible gene I–like helicases, cells are activated to produce type I IFN, which plays key roles in host antiviral innate immune response. However, excessive IFN production may induce immune disorders, and the mechanisms responsible for the regulation of type I IFN production have attracted much attention. Furthermore, type I IFN activates the downstream IFN/JAK/STAT pathway to modulate expression of a set of genes against viral infection, but whether these genes can feedback regulate type I IFN production is poorly understood. In this study, by screening the microRNAs modulated by viral infection in macrophages, we identified that microRNA (miR)-27a was significantly downregulated via the IFN/JAK/STAT1/runt-related transcription factor 1 pathway. Inducible downregulation of miR-27a, in turn, negatively regulated vesicular stomatitis virus–triggered type I IFN production, thus promoting vesicular stomatitis virus replication in macrophages. Mechanistically, we found that miR-27a directly targeted sialic acid–binding Ig-like lectin (Siglec)1 and E3 ubiquitin ligase tripartite motif–containing protein 27 (TRIM27), both of which were previously verified as negative regulators of type I IFN production. Furthermore, we constructed “Sponge” transgenic mice against miR-27a expression and found that Siglec1 and TRIM27 expression were elevated whereas type I IFN production was inhibited and viral replication was aggregated in vivo. Therefore, type I IFN–induced downregulation of miR-27a can upregulate Siglec1 and TRIM27 expression, feedback inhibiting type I IFN production in antiviral innate response. Our study outlines a new negative way to feedback regulate type I IFN production.
Год издания: 2015
Авторы: Qingliang Zheng, Jin Hou, Ye Zhou, Yingyun Yang, Xuetao Cao
Издательство: American Association of Immunologists
Источник: The Journal of Immunology
Ключевые слова: interferon and immune responses, MicroRNA in disease regulation, Cancer-related molecular mechanisms research
Другие ссылки: The Journal of Immunology (HTML)
PubMed (HTML)