MiR‐199a‐3p modulates the function of dendritic cells involved in transplantation tolerance by targeting CD86

Abstract

Dendritic cells (DCs) are key components of the immune system, serving as antigen‐presenting cells to activate adaptive immunity. Whereas mature DCs promote immune responses, immature DCs induce or maintain immunological tolerance by downregulating T‐cell responses. Therefore, DCs are potent antigen (Ag)‐presenting cells in the immune system. MicroRNAs are noncoding RNAs that posttranscriptionally regulate mRNA by binding the 3′‐untranslated region (UTR) of these molecules, modulating their expression. Many recent studies have suggested a potential role of miRNAs in DCs maturation and differentiation, but the exact mechanisms governing this process are unclear. How and whether miR‐199a‐3p affects DC maturation has not been investigated. Here, we found that MiR‐199a‐3p levels are correlated with DC maturation, inflammatory cytokine secretion, and PI3K/AKT/NF‐κB signaling pathway activity. In addition, we analyzed the stimulation of regulatory T‐cells by DCs. Through this work, we determined CD86 to be targeted by miR‐199a‐3p, thereby linking it to DC maturation. miR‐199a‐3p therefore directly inhibits CD86 expression via 3′‐UTR targeting, subsequently prolonging allograft survival in a mouse heart transplantation model. miR‐199a‐3p over‐expression may therefore be a potential therapeutic strategy for use in organ transplantation or patients with autoimmune diseases.

Pinpointing Functionally Relevant miRNAs in Classical Hodgkin Lymphoma Pathogenesis

“…There are no reports on miRNAs that regulate CD30, CD40, or CD86 and that have an inversed expression pattern in cHL [ 119 , 120 ]. However, a miRNA-dependent regulation of TNF-α has been shown for miR-130a-3p which is downregulated in cHL, supporting a potential role for this miRNA [ 98 ].…”

Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis

“…It was found that miR-199b-3p expression was increased in septic acute kidney injury models, and that miR-199b-3p binds to nuclear factor erythroid 2-related factor (NRF2), which is a transcription factor directly involved in the transcriptional activation of genes involved in cellular antioxidant responses that plays a central role in the pathogenesis of TB [ 44 , 45 ]. Furthermore, miR-199a-3p can mediate immune tolerance by regulating dendritic cells, leading to increased secretion of interleukin 10 as well as to the inhibition of the phosphatidylinositol 3-kinase/protein kinase B/nuclear factor kappa B pathway, and miR-16 was significantly upregulated in the serum of patients with TB compared with healthy controls [ 46 , 47 ]. In addition to miR-199b-3p and miR-199a-3p, other miRNAs have also been found to function as major components in cancer biology.…”

Kinetic Changes in B7 Costimulatory Molecules and IRF4 Expression in Human Dendritic Cells during LPS Exposure

“…In contrast, cytokines related to T-cell activation, IFN-γ and IL-2, had a maximum secretion peak at the most prolonged time evaluated, similarly to the CD86 and ICOS-L expression. This differential kinetic expression could be explained by other reported biological mechanisms affecting protein expression, such as post-translational modifications and miRNA regulation, which should be addressed further to explain the B7 dynamic expression [ 37 , 38 , 39 , 40 ].…”