title: Synergistic suppression of autoimmune arthritis through concurrent treatment with tolerogenic DC and MSC.
abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive immune-mediated joint deterioration. Current treatments are not antigen specific and are associated with various adverse. We have previously demonstrated that tolerogenic dendritic cells (Tol-DC) are potent antigen-specific immune regulators, which hold great promise in immunotherapy of autoimmune diseases. In this study, we aimed to develop new immunotherapy by combining Tol-DC and mesenchymal stem cells (MSC). We demonstrated that RelB gene silencing resulted in generation of Tol-DC that suppressed T cell responses and selectively promoted Treg generation. The combination of MSC synergized the tolerogenic capacity of Tol-DC in inhibition of T cell responses. In murine collagen-induced arthritis (CIA) model, we demonstrated that progression of arthritis was inhibited with administration of RelB gene-silenced Tol-DC or MSC. This therapeutic effect was remarkably enhanced with concurrent treatment of combination Tol-DC and MSC as demonstrated by improved clinical symptoms, decreased clinical scores and attenuated joint damage. These therapeutic effects were associated with suppression of CII-specific T cell responses, polarization of Th and inhibition of proinflammatory cytokines, and reduced cartilage degeneration. This study for the first time demonstrates a new approach to treat autoimmune inflammatory joint disease with concurrent treatment of RelB gene-silenced Tol-DC and MSC.
authors.affiliation: College of Basic Medical Sciences and Institute of Immunotherapy of Nanchang University, and Jiangxi Academy of Medical Sciences, Nanchang, China.|Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: College of Basic Medical Sciences and Institute of Immunotherapy of Nanchang University, and Jiangxi Academy of Medical Sciences, Nanchang, China.|Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Departments of Surgery, Pathology, and Oncology, University of Western Ontario, London, Canada.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zheng
authors.affiliation: College of Basic Medical Sciences and Institute of Immunotherapy of Nanchang University, and Jiangxi Academy of Medical Sciences, Nanchang, China.|Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Peng
authors.affiliation: College of Basic Medical Sciences and Institute of Immunotherapy of Nanchang University, and Jiangxi Academy of Medical Sciences, Nanchang, China.|Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, China.
authors.forename: Keng
authors.initials: K
authors.lastname: Yuan
authors.affiliation: Departments of Surgery, Pathology, and Oncology, University of Western Ontario, London, Canada.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Basic Medical Sciences and Institute of Immunotherapy of Nanchang University, and Jiangxi Academy of Medical Sciences, Nanchang, China.|Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, China.|Departments of Surgery, Pathology, and Oncology, University of Western Ontario, London, Canada.
authors.forename: Weiping
authors.initials: W
authors.lastname: Min
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D017690:Cell Transplantation / Q000379:methods*; D003713:Dendritic Cells / Q000502:physiology*; D004195:Disease Models, Animal; D020868:Gene Silencing; D007165:Immunosuppression Therapy / Q000379:methods; D007167:Immunotherapy / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D051841:Transcription Factor RelB / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C497594:Relb protein, mouse; D051841:Transcription Factor RelB