title: Fusion protein of tapasin and hepatitis B core antigen 18‑27 enhances T helper cell type 1/2 cytokine ratio and antiviral immunity by inhibiting suppressors of cytokine signaling family members 1/3 in hepatitis B virus transgenic mice.
abstract: Persistent hepatitis B virus (HBV) infection is characterized by a weak adaptive immune response, which is considered to be due to an imbalance of T helper cell types 1 and 2 (Th1/Th2). Suppressors of cytokine signaling (SOCS) family members, particularly SOCS1 and SOCS3, have been demonstrated to be important in the regulation of T cell differentiation. Previous studies by our group showed that the expressed and purified fusion protein of cytoplasmic transduction peptide (CTP) and HBV core antigen 18‑27 (HBcAg18‑27)‑tapasin was able to enter the cytoplasm of bone marrow‑derived dendritic cells (BMDCs), promoting the maturation of BMDCs and efficiently enhancing T cell immune responses in vitro. In the present study, HBcAg‑specific immune responses induced by CTP‑HBcAg18‑27‑tapasin in HBV were assessed in transgenic mice, and SOCS1 and SOCS3 were identified as negative regulators of this response. The Th1/Th2 cytokine ratio was analyzed by ELISA. The expression of T cell‑specific T‑box transcription factor (T‑bet) and GATA‑binding protein 3 (GATA‑3), SOCS1 and SOCS3 were detected by real‑time quantitative polymerase chain reaction and western blot analysis. The results demonstrated that CTP‑HBcAg18‑27‑tapasin significantly increased the Th1/Th2 cytokine ratio in HBV transgenic mice. CTP‑HBcAg18‑27‑tapasin immunization more efficiently suppressed the expression of serum hepatitis B surface antigen (HBsAg), HBV DNA as well as liver HBsAg and HBcAg in HBV transgenic mice. Furthermore, CTP‑HBcAg18‑27‑tapasin promotes T‑bet but reduces GATA‑3 expression. In addition, the expression of SOCS1 and SOCS3 was significantly downregulated in the CTP‑HBcAg18‑27‑tapasin group compared with the control groups. In conclusion, the present study demonstrated that CTP‑HBcAg18‑27‑tapasin enhanced the Th1/Th2 cytokine ratio and antiviral immunity by suppressing SOCS1/3 in HBV transgenic mice.
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhuo
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zang
authors.affiliation: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004279:DNA, Viral / Q000097:blood; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006509:Hepatitis B / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000097:blood / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology*; D007109:Immunity / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D004279:DNA, Viral; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D026901:Membrane Transport Proteins; D010455:Peptides; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D050826:Suppressor of Cytokine Signaling Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C107762:tapasin