Dexamethasone preconditioning improves the response of collagen-induced arthritis to treatment with short-term lipopolysaccharide-stimulated collagen-loaded dendritic cells

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Abstract

Background. Pharmacologically modulated dendritic cells (DCs) have been shown to restore tolerance in type II collagen-(CII-) induced arthritis (CIA). We examined the effect of dexamethasone (DXM) administration as a preconditioning agent, followed by an injection of lipopolysaccharide-(LPS-) stimulated and CII-loaded DCs on the CIA course. Methods. After CIA induction, mice pretreated with DXM were injected with 4-hour LPS-stimulated DCs loaded with CII (DXM/4hLPS/CII/DCs). Results. Mice injected with DXM/4hLPS/CII/DCs displayed significantly less severe clinical disease compared to animals receiving 4hLPS/CII/DCs alone or those in which only DXM was administered. Cytokine profile evaluation showed that CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups release higher IL-10 levels than those from mice receiving DXM alone or CIA mice. CD4+ T cells from all DC-treated groups showed less IL-17 release when compared to the CIA group. On the contrary, CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups released higher IFN-γ levels than those from CIA group. Conclusion. A combined treatment, including DXM preconditioning followed by an inoculation of short-term LPS-stimulated CII-loaded DCs, provides an improved strategy for attenuating CIA severity. Our results suggest that this benefit is driven by a modulation in the cytokine profile secreted by CD4+ T cells. © 2013 Corina Peña et al.

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Peña, C., Gárate, D., Contreras-Levicoy, J., Aravena, O., Catalán, D., & Aguillón, J. C. (2013). Dexamethasone preconditioning improves the response of collagen-induced arthritis to treatment with short-term lipopolysaccharide-stimulated collagen-loaded dendritic cells. Clinical and Developmental Immunology, 2013. https://doi.org/10.1155/2013/296031

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