Open Access Open Badges Research article

RNAi-mediated CD40-CD154 interruption promotes tolerance in autoimmune arthritis

Xiufen Zheng1, Motohiko Suzuki1, Xusheng Zhang1, Thomas E Ichim13, Fei Zhu2, Hong Ling1, Aminah Shunnar1, Michael H Wang1, Bertha Garcia1, Robert D Inman2* and Wei-Ping Min145*

Author affiliations

1 Departments of Surgery, Pathology, Microbiology and Immunology, University of Western Ontario, 1393 Western Road, London, Ontario, N6G 1G9, Canada

2 Division of Rheumatology, Department of Medicine, Toronto Western Hospital, University Health Network, 1E423 - 399 Bathurst Street, Toronto, Ontario, M5T 2S8, Canada

3 Medistem Inc, 9255 Towne Centre Drive, San Diego, CA 92121-3038, USA

4 Multi-Organ Transplant Program, London Health Sciences Centre, 339 Windermere Road, London, Ontario, N6A, 5A5, Canada

5 Transplantation and Regenerative Medicine, Lawson Health Research Institute, 339 Windermere Road, London, Ontario, N6A, 5A5, Canada

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Citation and License

Arthritis Research & Therapy 2010, 12:R13  doi:10.1186/ar2914

Published: 26 January 2010



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.


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.


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.


These studies support the feasibility of transient gene silencing at a systemic level as a mechanism of resetting autoreactive immunity.