title: Dendritic cells that highly express SOCS1 induce T-cell hypo-responsiveness and prolong islet allograft survival.
abstract: The capability of dendritic cells (DCs) to induce an immune response or immune tolerance is dependent on their status. Suppressor of cytokine signaling 1 (SOCS1) is a pivotal regulator that participates in negative feedback of the JAK-STAT pathway, which plays a key role in the differentiation, activation, and maturation of DCs. DCs that highly express SOCS1 may modulate DCs, and induce immune anergy or immune tolerance. In this study, we transduced DCs with the recombinant adenovirus Ad5F35 to highly express SOCS1. The mechanisms by which DC-SOCS1 induces T-cell hypo-responsiveness were analyzed in vivo and in vitro. The data demonstrate that recipients treated with DC-SOCS1 had long islet allograft survival times, with a reduction of Th1 and Tc1 in both spleen and draining lymph nodes in vivo. In vitro assay revealed that DCs transduced with SOCS1 had low expression of major histocompatibility and costimulatory molecules, and potentiated the ability of DC-SOCS1 to induce T-cell hypo-responsiveness. Therefore, genetic modification of DCs with SOCS1 affects DC activation and maturation, inhibits T-cell proliferation and induces hypo-responsiveness, and prolongs islet allograft survival.
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xinjun
authors.initials: X
authors.lastname: Lu
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Maogen
authors.initials: M
authors.lastname: Chen
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xuzhi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Linwei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: mddrh81@163.com.
authors.forename: Ronghai
authors.initials: R
authors.lastname: Deng
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: anhuimayi2002@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006085:Graft Survival / Q000235:genetics; D007108:Immune Tolerance; D016381:Islets of Langerhans Transplantation; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D019076:Transgenes / Q000235:genetics; D014184:Transplantation, Homologous
chemical_list: C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein
keywords: Dendritic cell; Immune tolerance; Islet transplant; SOCS1; T-cell hypo-responsiveness