Chicken miR-126-5p Negatively Regulates Antiviral Innate Immunity By Targeting TRAF3

DOI: https://doi.org/10.21203/rs.3.rs-655390/v1

Abstract

Background Innate immunity plays an essential role in preventing the invasion of pathogenic microorganisms. However, innate immunity is a double-edged sword, whose excessively activated is detrimental to immune homeostasis and even leads to "cytokine storm" of the infected host. A series of negative regulatory mechanisms are developed by the host to balance the immune response. Here, we report a negative regulatory mechanism of chicken innate immunity mediated by miRNA.

Results In this study we found that the miR-126-5p is markedly up-regulated in RNA virus infected chickens in GEO database. Then, the upregulation of the miR-126-5p by RNA virus was further verified via both cell model and in vivo test. Overexpression of miR-126-5p significantly inhibits the expression of interferon related genes and inflammatory cytokines evoked by RNA virus. The opposite result was achieved after knocking down miR-126-5p expression. Bioinformatics analysis indicated TRAF3 as the candidate target gene of miR-126-5p, and experimental evidence, such as the effects of miR-126-5p on the endogenous expression of TRAF3, and the effect of miR-126-5p on TRAF3 3'UTR drove luciferase reporter assay, were provided to further verify that miR-126-5p targets TRAF3. Furthermore, we demonstrated that miR-126-5p negatively regulates innate immunity by blocking the MAVS-TRAF3-TBK1 axis, with co-expression assay.

Conclusion Our results suggest that miR-126-5p is involved in the negative regulation of the chicken innate immunity, which might contribute to maintaining immune balance.

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