title: Regulation of T cell proliferation by JMJD6 and PDGF-BB during chronic hepatitis B infection.
abstract: T cell functional exhaustion during chronic hepatitis B virus (HBV) infection may contribute to the failed viral clearance; however, the underlying molecular mechanisms remain largely unknown. Here we demonstrate that jumonji domain-containing protein 6 (JMJD6) is a potential regulator of T cell proliferation during chronic HBV infection. The expression of JMJD6 was reduced in T lymphocytes in chronic hepatitis B (CHB) patients, and this reduction in JMJD6 expression was associated with impaired T cell proliferation. Moreover, silencing JMJD6 expression in primary human T cells impaired T cell proliferation. We found that JMJD6 promotes T cell proliferation by suppressing the mRNA expression of CDKN3. Furthermore, we have identified platelet derived growth factor-BB (PDGF-BB) as a regulator of JMJD6 expression. PDGF-BB downregulates JMJD6 expression and inhibits the proliferation of human primary T cells. Importantly, the expression levels of JMJD6 and PDGF-BB in lymphocytes from CHB patients were correlated with the degree of liver damage and the outcome of chronic HBV infection treatment. Our results demonstrate that PDGF-BB and JMJD6 regulate T cell function during chronic HBV infection and may provide insights for the treatment strategies for CHB patients.
authors.affiliation: 1] MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, People's Republic of China [2].
authors.forename: Cai-Feng
authors.initials: CF
authors.lastname: Chen
authors.affiliation: 1] Center for Infection and Immunity, YouAn Hospital, The Beijing Capital Medical University, Beijing, China [2].
authors.forename: Xia
authors.initials: X
authors.lastname: Feng
authors.affiliation: 1] Center for Infection and Immunity, YouAn Hospital, The Beijing Capital Medical University, Beijing, China [2].
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Liao
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Jin
authors.affiliation: Diagnosis and Treatment Center of Liver Fibrosis, 302 Hospital, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Gong
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jing-Jun
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Yuan
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Zhao
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Ding
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Diagnosis and Treatment Center of Liver Fibrosis, 302 Hospital, Beijing, China.
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Chen
authors.affiliation: Biomedical Analysis Center, The Third Military Medical University, Chongqing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.affiliation: Center for Infection and Immunity, YouAn Hospital, The Beijing Capital Medical University, Beijing, China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Yan
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D000077214:Becaplermin; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism*; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000998:Antiviral Agents; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D000077214:Becaplermin; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; C084429:CDKN3 protein, human; D054637:Dual-Specificity Phosphatases