PMID- 31448543 OWN - NLM STAT- MEDLINE DCOM- 20200601 LR - 20200601 IS - 2059-2310 (Electronic) IS - 2059-2302 (Linking) VI - 94 IP - 6 DP - 2019 Dec TI - MiR-199a-3p modulates the function of dendritic cells involved in transplantation tolerance by targeting CD86. PG - 493-503 LID - 10.1111/tan.13677 [doi] AB - 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-kappaB 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. CI - (c) 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Xiong, Ali AU - Xiong A AUID- ORCID: 0000-0003-3309-654X AD - Department of Medical Laboratory, The Central Hospital of Wuhan, TongJi Medical College, Huazhong University of Science and Technology, WuHan, China. FAU - Wang, Jing AU - Wang J AD - Department of Medical Laboratory, The Central Hospital of Wuhan, TongJi Medical College, Huazhong University of Science and Technology, WuHan, China. FAU - Mao, Xiao Li AU - Mao XL AD - Department of Medical Laboratory, The Central Hospital of Wuhan, TongJi Medical College, Huazhong University of Science and Technology, WuHan, China. FAU - Jiang, Yi AU - Jiang Y AD - Department of Medical Laboratory, The Central Hospital of Wuhan, TongJi Medical College, Huazhong University of Science and Technology, WuHan, China. FAU - Fan, Yue AU - Fan Y AD - Department of Medical Laboratory, The Central Hospital of Wuhan, TongJi Medical College, Huazhong University of Science and Technology, WuHan, China. LA - eng GR - 31500729/National Natural Science Foundation of China/International GR - 20130142120056/US/United States/United States GR - 20130142120056/US/United States/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190903 PL - England TA - HLA JT - HLA JID - 101675570 RN - 0 (3' Untranslated Regions) RN - 0 (B7-2 Antigen) RN - 0 (Cd86 protein, mouse) RN - 0 (MicroRNAs) RN - 0 (Mirn199 microRNA, mouse) SB - IM MH - 3' Untranslated Regions/genetics MH - Allografts/immunology MH - Animals MH - B7-2 Antigen/*genetics/metabolism MH - Cell Differentiation/genetics MH - Cell Proliferation/genetics MH - Cells, Cultured MH - Dendritic Cells/metabolism/*physiology MH - Gene Expression Regulation MH - Graft Survival/genetics/immunology MH - Heart Transplantation MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - MicroRNAs/genetics/*physiology MH - Transplantation Tolerance/*genetics/*immunology OTO - NOTNLM OT - CD86 OT - NF-kappaB OT - dendritic cells OT - miR-199a-3p OT - transplantation EDAT- 2019/08/27 06:00 MHDA- 2020/06/02 06:00 CRDT- 2019/08/27 06:00 PHST- 2019/02/02 00:00 [received] PHST- 2019/08/06 00:00 [revised] PHST- 2019/08/23 00:00 [accepted] PHST- 2019/08/27 06:00 [pubmed] PHST- 2020/06/02 06:00 [medline] PHST- 2019/08/27 06:00 [entrez] AID - 10.1111/tan.13677 [doi] PST - ppublish SO - HLA. 2019 Dec;94(6):493-503. doi: 10.1111/tan.13677. Epub 2019 Sep 3.