Dexamethasone Preconditioning Improves the Response of Collagen-Induced Arthritis to Treatment with Short-Term Lipopolysaccharide-Stimulated Collagen-Loaded Dendritic Cells

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+Tcells fromallDC-treatedgroups showed less IL-17 releasewhencompared to theCIAgroup.On the contrary, CD4+T cells fromDXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups released higher IFN-𝛾 levels than those fromCIA group. Conclusion. A combined treatment, including DXMpreconditioning followed by an inoculation of short-termLPS-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.