PMID- 26109844 OWN - NLM STAT- MEDLINE DCOM- 20160201 LR - 20181113 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 9 DP - 2015 TI - Osteopontin promotes dendritic cell maturation and function in response to HBV antigens. PG - 3003-16 LID - 10.2147/DDDT.S81656 [doi] AB - PURPOSE: 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. CONCLUSION: 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. FAU - Cui, Guangying AU - Cui G AD - 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. FAU - Chen, Jianing AU - Chen J AD - 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. FAU - He, Jianqin AU - He J AD - 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. FAU - Lu, Chong AU - Lu C AD - 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. FAU - Wei, Yingfeng AU - Wei Y AD - 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. FAU - Wang, Lin AU - Wang L AD - 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. FAU - Xu, Xuejun AU - Xu X AD - Department of Oral Orthodontics, Affiliated Stomatology Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China. FAU - Li, Lanjuan AU - Li L AD - 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. FAU - Uede, Toshimitsu AU - Uede T AD - Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. FAU - Diao, Hongyan AU - Diao H AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150612 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (CD11c Antigen) RN - 0 (Hepatitis B Antigens) RN - 0 (Hepatitis B e Antigens) RN - 106441-73-0 (Osteopontin) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Adoptive Transfer MH - Adult MH - Animals MH - Bone Marrow Cells/drug effects MH - CD11c Antigen/metabolism MH - Coculture Techniques MH - Dendritic Cells/*drug effects/pathology MH - Female MH - Hepatitis B Antigens/*pharmacology MH - Hepatitis B e Antigens/blood MH - Hepatitis C/drug therapy/pathology MH - Humans MH - Interleukin-12/biosynthesis MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Monocytes/drug effects/immunology MH - Osteopontin/*genetics/*therapeutic use MH - Th1 Cells/drug effects/immunology PMC - PMC4472071 OTO - NOTNLM OT - dendritic cells OT - hepatitis B virus OT - osteopontin EDAT- 2015/06/26 06:00 MHDA- 2016/02/02 06:00 PMCR- 2015/06/12 CRDT- 2015/06/26 06:00 PHST- 2015/06/26 06:00 [entrez] PHST- 2015/06/26 06:00 [pubmed] PHST- 2016/02/02 06:00 [medline] PHST- 2015/06/12 00:00 [pmc-release] AID - dddt-9-3003 [pii] AID - 10.2147/DDDT.S81656 [doi] PST - epublish SO - Drug Des Devel Ther. 2015 Jun 12;9:3003-16. doi: 10.2147/DDDT.S81656. eCollection 2015.