title: Tolerogenic dendritic cells generated by RelB silencing using shRNA prevent acute rejection.
abstract: It is well known that adoptive transfer of donor-derived tolerogenic dendritic cells (DCs) helps to induce immune tolerance. RelB, one of NF-κB subunits, is a critical element involved in DC maturation. In the present study, our results showed tolerogenic DCs could be acquired via silencing RelB using small interfering RNA. Compared with imDCs, the tolerogenic DCs had more potent ability to inhibit mixed lymphocyte reaction (MLR) and down-regulate Th1 cytokines and prompt the production of Th2 cytokines. They both mediated immune tolerance via the increased of T cell apoptosis and generation of regulatory T cells. Administration of donor-derived tolerogenic DCs significantly prevented the allograft rejection and prolonged the survival time in a murine heart transplantation model. Our results demonstrate donor-derived, RelB-shRNA induced tolerogenic DCs can significantly induce immune tolerance in vitro and in vivo.
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, China.
authors.forename: Heng-cheng
authors.initials: HC
authors.lastname: Zhu
authors.forename: Tao
authors.initials: T
authors.lastname: Qiu
authors.forename: Xiu-heng
authors.initials: XH
authors.lastname: Liu
authors.forename: Wang-chao
authors.initials: WC
authors.lastname: Dong
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Weng
authors.forename: Chun-hai
authors.initials: CH
authors.lastname: Hu
authors.forename: You-lin
authors.initials: YL
authors.lastname: Kuang
authors.forename: Rui-hui
authors.initials: RH
authors.lastname: Gao
authors.forename: Chao
authors.initials: C
authors.lastname: Dan
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D034741:RNA, Small Interfering; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D051841:Transcription Factor RelB / Q000235:genetics*
chemical_list: D016207:Cytokines; D034741:RNA, Small Interfering; C497594:Relb protein, mouse; D051841:Transcription Factor RelB