Introduction: We have previously demonstrated that ex vivo inhibition of costimulatory molecules on antigen-pulsed dendritic cells (DCs) can be useful for induction of antigen-specific immune deviation and suppression of autoimmune arthritis in the collagen induced arthritis (CIA) model. The current study evaluated a practical method of immune modulation through temporary systemic inhibition of the costimulatory molecule CD40.Methods: Mice with collagen II (CII)-induced arthritis (CIA) were administered siRNA targeting the CD40 molecule. Therapeutic effects were evaluated by clinical symptoms, histopathology, Ag-specific T cell and B cell immune responses.Results: Systemic administration of CD40-targeting siRNA can inhibit antigen-specific T cell response to collagen II, as well as prevent pathogenesis of disease in both a pre- and post-immunization manner in the CIA model. Disease amelioration was associated with suppression of Th1 cytokines, attenuation of antibody production, and upregulation of T regulatory cells.Conclusions: These studies support the feasibility of transient gene silencing at a systemic level as a mechanism of resetting autoreactive immunity. © 2010 Zheng et al.; licensee BioMed Central Ltd.
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Zheng, X., Suzuki, M., Zhang, X., Ichim, T. E., Zhu, F., Ling, H., … Min, W. P. (2010). RNAi-mediated CD40-CD154 interruption promotes tolerance in autoimmune arthritis. Arthritis Research and Therapy, 12(1). https://doi.org/10.1186/ar2914
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