AI Article Synopsis
- The study investigates how temporarily inhibiting the costimulatory molecule CD40 can modulate the immune response in a mouse model of autoimmune arthritis.
- The researchers used siRNA targeting CD40 in mice with collagen-induced arthritis to assess its therapeutic effects on clinical symptoms and immune responses.
- Results show that this approach effectively reduces disease severity by dampening T cell responses and promoting regulatory T cells, suggesting potential for resetting harmful immune reactions.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875641 | PMC |
| http://dx.doi.org/10.1186/ar2914 | DOI Listing |
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