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Sci Rep. 2017 Feb 23;7:43188. doi: 10.1038/srep43188.

Synergistic suppression of autoimmune arthritis through concurrent treatment with tolerogenic DC and MSC.

Li R1,2, Zhang Y1,2, Zheng X3, Peng S1,2, Yuan K1,2, Zhang X3, Min W1,2,3.

Author information

1
College of Basic Medical Sciences and Institute of Immunotherapy of Nanchang University, and Jiangxi Academy of Medical Sciences, Nanchang, China.
2
Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, China.
3
Departments of Surgery, Pathology, and Oncology, University of Western Ontario, London, Canada.

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.

PMID:
28230210
PMCID:
PMC5322386
DOI:
10.1038/srep43188
[Indexed for MEDLINE]
Free PMC Article

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