PMID- 28063705 OWN - NLM STAT- MEDLINE DCOM- 20171208 LR - 20171213 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 35 IP - 5 DP - 2017 Feb 1 TI - H9N2 avian influenza virus enhances the immune responses of BMDCs by down-regulating miR29c. PG - 729-737 LID - S0264-410X(16)31287-7 [pii] LID - 10.1016/j.vaccine.2016.12.054 [doi] AB - Avian influenza virus (AIV) of the subtypes H9 and N2 is well recognised and caused outbreaks-due to its high genetic variability and high rate of recombination with other influenza virus subtypes. The pathogenicity of H9N2 AIV depends on the host immune response. Dendritic cells (DCs) are major antigen presenting cells that can significantly inhibit H9N2 AIV replication. MicroRNAs (miRNAs) influence the ability of DCs to present antigens, as well as the ability of AIVs to infect host cells and replicate. Here, we studied the molecular mechanism underlying the miRNA-mediated regulation of immune function of mouse DCs. We first screened for and verified the induction of miRNAs in DCs after H9N2 AIVstimulation. We also constructed miR29c, miR339 and miR222 over-expression vector and showed that only the induction of miR29c lead to a hugely increased expression of surface marker MHCII and CD40. Whilst the inhibition of miR29c, miR339 and miR222 in mouse DCs would repressed the expression of DCs surface markers. Moreover, we found that miR29c stimulation not only up-regulate MHCII and CD40, but also enhance the ability of DCs to activate lymphocytes and secrete cytokines IL-6 or TNF-a. Furthermore, we found that Tarbp1 and Rfx7 were targeted and repressed by miR29c. Finally, we revealed that the inhibition of miR29c marvelously accelerated virus replication. Together, our data shed new light on the roles and mechanisms of miR29c in regulating DC function and suggest new strategies for combating AIVs. CI - Copyright (c) 2016. Published by Elsevier Ltd. FAU - Lin, Jian AU - Lin J AD - College of Life Science, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: linjian@njau.edu.cn. FAU - Xia, Jing AU - Xia J AD - College of Life Science, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: 2014816155@njau.edu.cn. FAU - Chen, Ya T AU - Chen YT AD - College of Life Science, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: 2013816153@njau.edu.cn. FAU - Zhang, Ke Y AU - Zhang KY AD - College of Life Science, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: keyunzhang@njau.edu.cn. FAU - Zeng, Yan AU - Zeng Y AD - College of Life Science, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: zengyan@njau.edu.cn. FAU - Yang, Qian AU - Yang Q AD - College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: zxbyq@njau.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170104 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (CD40 Antigens) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Interleukin-6) RN - 0 (MIRN29 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Oligoribonucleotides, Antisense) RN - 0 (RNA-Binding Proteins) RN - 0 (Regulatory Factor X Transcription Factors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (interleukin-6, mouse) RN - 136628-24-5 (trans-activation responsive RNA-binding protein) SB - IM MH - Animals MH - Antigen Presentation MH - Bone Marrow Cells/immunology/virology MH - CD40 Antigens/genetics/immunology MH - Dendritic Cells/*immunology/virology MH - Gene Expression Regulation MH - Histocompatibility Antigens Class II/genetics/immunology MH - *Host-Pathogen Interactions MH - Influenza A Virus, H9N2 Subtype/*genetics/immunology/pathogenicity MH - Interleukin-6/genetics/*immunology MH - Lymphocyte Activation MH - Lymphocytes/immunology/virology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/agonists/antagonists & inhibitors/*genetics/immunology MH - Oligoribonucleotides, Antisense/genetics/metabolism MH - Primary Cell Culture MH - RNA-Binding Proteins/genetics/immunology MH - Regulatory Factor X Transcription Factors/genetics/immunology MH - Signal Transduction MH - Tumor Necrosis Factor-alpha/genetics/*immunology MH - Virulence MH - Virus Replication OTO - NOTNLM OT - Dendritic cells OT - H9N2 AIV OT - Immune regulation OT - Target gene OT - miR29c EDAT- 2017/01/09 06:00 MHDA- 2017/12/09 06:00 CRDT- 2017/01/09 06:00 PHST- 2016/09/18 00:00 [received] PHST- 2016/12/19 00:00 [revised] PHST- 2016/12/22 00:00 [accepted] PHST- 2017/01/09 06:00 [pubmed] PHST- 2017/12/09 06:00 [medline] PHST- 2017/01/09 06:00 [entrez] AID - S0264-410X(16)31287-7 [pii] AID - 10.1016/j.vaccine.2016.12.054 [doi] PST - ppublish SO - Vaccine. 2017 Feb 1;35(5):729-737. doi: 10.1016/j.vaccine.2016.12.054. Epub 2017 Jan 4.