title: Regulation of T cell function by microRNA-720.
abstract: Chronic hepatitis B virus (HBV) infection is a major global health burden. Functional exhaustion and numerical reduction of HBV-specific cytotoxic T lymphocytes (CTLs) in the liver and peripheral blood limit anti-HBV CTL activity in patients with chronic HBV infection (CHB). However, the ongoing anti-HBV CD8(+) T cell responses in the lymphoid organs are largely unknown due to the infeasibility of obtaining lymphoid organs from CHB patients. Here we demonstrate that the percentage of HBV-specific CD8(+) T cells is higher in the spleen of CHB patients than that from peripheral blood and liver. Although they do respond to TCR stimulation and produce IFNγ, the cells proliferate poorly. Furthermore, miR-720 expression is upregulated in HBV-specific CD8(+) T cells. Overexpression of miR-720 in primary human CD8(+) T cells inhibits TCR stimulation-induced proliferation. We also demonstrate that TGFβ sustains miR-720 upregulation after TCR stimulation, and blood TGFβ levels are associated with the outcome of type I interferon treatment of CHB patients. Thus, therapies targeting miR-720 may help restore impaired immunity in CHB patients.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ji
authors.affiliation: Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Chen
authors.affiliation: Beijing YouAn Hospital, Beijing 100069, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Feng
authors.affiliation: Key Laboratory of Systems Biology of Pathogens, Ministry of Health, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100730, China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Gong
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.affiliation: Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Li
authors.affiliation: Key Laboratory of Systems Biology of Pathogens, Ministry of Health, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100730, China.
authors.forename: Cai-Feng
authors.initials: CF
authors.lastname: Chen
authors.affiliation: Key Laboratory of Systems Biology of Pathogens, Ministry of Health, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100730, China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Zhao
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Li
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Li
authors.affiliation: Beijing YouAn Hospital, Beijing 100069, China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Yan
authors.affiliation: Department of Medicine, Pathology and Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Gregory
authors.initials: G
authors.lastname: Sempowski
authors.affiliation: Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C568636:MIRN720 microRNA, human; D035683:MicroRNAs; D011948:Receptors, Antigen, T-Cell; D016212:Transforming Growth Factor beta