title: Overexpression of Jagged-1 combined with blockade of CD40 pathway prolongs allograft survival.
abstract: Dendritic cells (DCs) have the tolerogenic potential to regulate adaptive immunity and induce allografts acceptance. Here we investigated whether blockade of the CD40 pathway could enhance the immune tolerance induced by DC2.4 cells modified to express Jagged-1 (JAG1-DC) in heart transplantation. Results showed that JAG1-DC treatment combined with anti-CD40L monoclonal antibody (mAb) administration significantly prolonged cardiac allograft survival in mice, with long-term survival (>110 days) of 50% of the allografts in the recipients. The therapy specifically inhibited the immune response, induced alloantigen-specific T-cell hyporesponsiveness, upregulated transforming growth factor-β synthesis and increased the population of regulatory T cells (Tregs) driven by Jagged-1-Notch activation. These results highlight the potential application of gene therapy to induce alloantigen-specific Tregs effectively by providing the Jagged-1 stimulation.
authors.affiliation: Organ Transplantation Institute, Xiamen University, Fujian Province, P.R. China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Organ Transplantation Institute, Xiamen University, Fujian Province, P.R. China.
authors.forename: Weili
authors.initials: W
authors.lastname: Chen
authors.affiliation: Organ Transplantation Institute, Xiamen University, Fujian Province, P.R. China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Li
authors.affiliation: Basic Medical Department of Medical College, Xiamen University, Fujian Province, P.R. China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Yan
authors.affiliation: Organ Transplantation Institute, Xiamen University, Fujian Province, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Organ Transplantation Institute, Xiamen University, Fujian Province, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Jin
authors.affiliation: Basic Medical Department of Medical College, Xiamen University, Fujian Province, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Organ Transplantation Institute, Xiamen University, Fujian Province, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Gao
authors.affiliation: Organ Transplantation Institute, Xiamen University, Fujian Province, P.R. China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Ma
authors.affiliation: Organ Transplantation Institute, Xiamen University, Fujian Province, P.R. China.
authors.forename: Shuangyue
authors.initials: S
authors.lastname: Xu
authors.affiliation: Organ Transplantation Institute, Xiamen University, Fujian Province, P.R. China.
authors.forename: Zhongquan
authors.initials: Z
authors.lastname: Qi
mesh_terms: D064591:Allografts / Q000276:immunology*; D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051880:Receptors, Notch / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D002135:Calcium-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D016212:Transforming Growth Factor beta; D023201:CD40 Ligand