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MiR‐199a‐3p modulates the function of dendritic cells involved in transplantation tolerance by targeting CD86
Author(s) -
Xiong Ali,
Wang Jing,
Mao Xiao Li,
Jiang Yi,
Fan Yue
Publication year - 2019
Publication title -
hla
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.347
H-Index - 99
eISSN - 2059-2310
pISSN - 2059-2302
DOI - 10.1111/tan.13677
Subject(s) - cd86 , microrna , immune tolerance , transplantation , immune system , microbiology and biotechnology , dendritic cell , biology , pi3k/akt/mtor pathway , acquired immune system , cytokine , immunology , t cell , signal transduction , cancer research , medicine , gene , genetics , surgery
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.