title: Osteopontin promotes dendritic cell maturation and function in response to HBV antigens.
abstract: OBJECTIVE
  Dendritic cells (DCs) play critical roles in promoting innate and adaptive immunity in microbial infection. Functional impairment of DCs may mediate the suppression of viral-specific T-cell immune response in chronic hepatitis B (CHB) patients. Osteopontin (OPN) is involved in several liver diseases and infectious diseases. However, whether OPN affects DC function in hepatitis B virus (HBV) infection is unknown.
  
  
  METHODS
  Twenty CHB patients and 20 healthy volunteers were recruited. OPN secreted by DCs was compared. Peripheral blood mononuclear cells cultured with OPN antibody were examined to study the costimulatory molecular expression and interleukin (IL)-12 production of DCs after HBV antigenic stimulation. OPN-deficient mice were used to investigate the influence of OPN on DC maturation and function after HBV antigenic stimulation in vitro and in vivo. Exogenous OPN was administrated to further verify the functioning of DCs from CHB patients upon HBV antigenic stimulation.
  
  
  RESULTS
  We found that OPN production of DCs from CHB patients was significantly lower than those from healthy volunteers. The absence of OPN impaired IL-12 production and costimulatory molecular expression of DCs upon stimulation with HBV antigens. Defective DC function led to reduced activation of Th1 response to HBV antigens. In addition, OPN deficiency in DCs reduced the HBV antigen-induced inflammatory response in the liver of mice. Importantly, OPN administration significantly promoted the maturation of DCs from CHB patients in vitro.
  
  
  CONCLUSIONS
  These findings suggested that OPN could improve the maturation and functioning of DCs in the immune response to HBV antigens, which might be useful to further improve the effect of DC vaccine.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China ; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Cui
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China ; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China ; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Jianqin
authors.initials: J
authors.lastname: He
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China ; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Chong
authors.initials: C
authors.lastname: Lu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China ; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China ; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Oral Orthodontics, Affiliated Stomatology Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China ; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Lanjuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China ; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Diao
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D039521:CD11c Antigen / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006511:Hepatitis B Antigens / Q000494:pharmacology*; D006513:Hepatitis B e Antigens / Q000097:blood; D006526:Hepatitis C / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D053495:Osteopontin / Q000235:genetics* / Q000627:therapeutic use*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D039521:CD11c Antigen; D006511:Hepatitis B Antigens; D006513:Hepatitis B e Antigens; D053495:Osteopontin; D018664:Interleukin-12
keywords: dendritic cells; hepatitis B virus; osteopontin