Positive regulation of innate immune response by miRNA-let-7a-5p

Abstract

Background: We have hypothesized that different factors are involved in the severity of ACD and AD because some but not all patients with atopic dermatitis (AD) present with allergic conjunctival disease (ACD) including severe types such as atopic keratoconjunctivitis (AKC) with/without giant papillae. We previously reported that plasma miR-628-3p was up-regulated in AD with severe ACD, but not in severe AD without severe ACD or in our healthy controls. In this study, to investigate the pathogenesis of AD with and without severe ACD, we performed comprehensive plasma miRNA analysis and studied the function of some miRNAs which were significantly up-regulated in ACD.Methods: Transcriptomics analysis of miRNA was performed using the microarray platform from the plasma of nine individuals (AD, severe ACD, controls: n = 3 each). To confirm up-regulation of the 12 miRNAs of the eight miRNA groups we focused on, we performed quantitative miRNA polymerase chain reaction (PCR) assays using 80 plasma samples (AD: 23, severe ACD: 17, controls: 40). To study the function of the eight miRNAs which were significantly up-regulated in ACD, we transfected their mimic to THP-1 cells, a monocyte cell line, and performed comprehensive gene expression analysis of them. The up-regulation of gene expression of interest in transfected THP-1 cells with the hsa-let-7a-5p miRNA mimic was confirmed by quantitative RT-qPCR assay.Results: Quantitative miRNA PCR assays showed that hsa-let-7a-5p, hsa-let-7days-3p, hsa-let-7e-5p, and hsa-miR-151a-5p were significantly up-regulated in both AD-ACD+ and AD-ACD- as were hsa-miR-130a-3p, hsa-miR-151a-3p, has-miR-27b-3p, and hsa-miR-146a-5p in AD-ACD+ but not in AD-ACD-. The functions of each miRNA were investigated by comprehensive gene expression analysis of THP-1 cells transfected with each miRNA mimic. Of the eight miRNAs, hsa-let-7a-5p, hsa-let-7e-5p, has-miR-27b-3p, and hsa-miR-146a-5p mimic-transfected THP-1 cells showed the up-regulation of CXCL10 (IP-10; interferon gamma-induced protein 10), which might be one of the innate immune-related genes. Quantitative RT-qPCR assays of transfected THP-1 cells with the hsa-let-7a-5p miRNA mimic showed that the 17 genes up-regulated more than 10-fold in the comprehensive gene expression analysis, and TLR3, RIG-I, and MDA5, important innate immune-related genes, were significantly up-regulated. TNFSF13B, AIM2, USP41, STAP1, GBP4, CCL8, and IFI27, reportedly down-regulated by the hsa-miR-628-3p mimic, were also significantly up-regulated in the transfected cells.Conclusion: Hsa-let-7a-5p, which was significantly up-regulated in AD-ACD+ and AD-ACD-, could positively regulate the important innate immune-related genes such as TLR3, RIG-I, and MDA5. It is possible that in an allergic disease such as atopic keratoconjunctivitis and/or dermatitis, innate immune responses might be positively regulated by hsa-let-7a-5p in the plasma.

Ruminal microbiota-host crosstalks promote ruminal epithelial development in neonatal lambs with alfalfa hay introduction

“…In the MEbrown module, cell division, epithelial cell differentiation, and positive regulation of innate immune response are prominently featured. This indicates that the introduction of alfalfa hay induces significant changes in the pathways related to epithelial cell proliferation and development ( 70 , 71 ). This also explains the reasons behind the alterations in rumen papillae width and length.…”

Identification of ribosomal protein family as immune-cell-related biomarkers of NAFLD by bioinformatics and experimental analyses

“…Some of these molecules have been reported to be associated with immune reactions. For example, hsa-let-7a-5p could positively regulate the important innate immune-related genes such as TLR3, RIG-I, and MDA5, thus promoting innate immune responses (57). LncRNA MIAT correlated with immune infiltrates in HCC and targeted miR-411-5p/STAT3/PD-L1 axis mediating HCC immune response (58,59).…”

Intrinsic Effects of Exposome in Atopic Dermatitis: Genomics, Epigenomics and Regulatory Layers

“…MiR-223 was found to be upregulated in patients’ whole blood cells and is involved in hematopoietic lineage differentiation processes and platelet activation, displaying a diverse expression profile in complex diseases [ 62 , 63 ]. In addition, central miRNAs associated with various inflammatory disorders, such as miR-146a and miR-155 , were found to exhibit their primary mechanism of action in the pro-inflammatory NF-κB pathway [ 64 , 65 , 66 , 67 , 68 ]. Interestingly, the regulatory landscape of AD shares molecular similarities with several cancer types, with over-expression of miR-151 , an oncogenic miRNA that facilitates metastasis, and repression of miR-451a and miR-194-5p , suggesting potential consensus mechanisms that could serve as early, identifiable risk factors in preventive medicine [ 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ].…”