title: Decline of miR-124 in myeloid cells promotes regulatory T-cell development in hepatitis C virus infection.
abstract: Myeloid-derived suppressor cells (MDSCs) and microRNAs (miRNAs) contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood. We have recently shown marked expansion of MDSCs that promote regulatory T (Treg) cell development in patients with chronic hepatitis C virus (HCV) infection. Here we further investigated whether the HCV-induced expansion of MDSCs and Treg cells is regulated by an miRNA-mediated mechanism. The RNA array analysis revealed that six miRNAs were up-regulated and six miRNAs were down-regulated significantly in myeloid cells during HCV infection. Real-time RT-PCR confirmed the down-regulation of miR-124 in MDSCs from HCV patients. Bioinformatic analysis suggested that miR-124 may be involved in the regulation of signal transducer and activator of transcription 3 (STAT-3), which was overexpressed in MDSCs from HCV patients. Notably, silencing of STAT-3 significantly increased the miR-124 expression, whereas reconstituting miR-124 decreased the levels of STAT-3, as well as interleukin-10 and transforming growth factor-β, which were overexpressed in MDCSs, and reduced the frequencies of Foxp3+Treg cells that were developed during chronic HCV infection. These results suggest that reciprocal regulation of miR-124 and STAT-3 in MDSCs promotes Treg cell development, thus uncovering a novel mechanism for the expansion of MDSC and Treg cells during HCV infection.
authors.affiliation: Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Jun P
authors.initials: JP
authors.lastname: Ren
authors.affiliation: Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Centre for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Shun B
authors.initials: SB
authors.lastname: Ning
authors.affiliation: Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Gazzar
authors.affiliation: Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Hepatitis (HCV/HIV) Program, Department of Veterans Affairs, James H. Quillen VA Medical Center, Johnson City, TN, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Moorman
authors.affiliation: Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Hepatitis (HCV/HIV) Program, Department of Veterans Affairs, James H. Quillen VA Medical Center, Johnson City, TN, USA.
authors.forename: Zhi Q
authors.initials: ZQ
authors.lastname: Yao
mesh_terms: D002478:Cells, Cultured; D019295:Computational Biology; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000072737:Myeloid-Derived Suppressor Cells / Q000502:physiology* / Q000821:virology; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
keywords: hepatitis C virus; microRNA-124; myeloid-derived suppressor cells; regulatory T cells; signal transducer and activator of transcription 3