The role of nitric oxide on the supressive activity of dendritic cells modulated with chloroquine

Abstract

Dendritic cells (DCs) are capable to direct the immune response towards an inflammatory or anti-inflammatory context, depending on its maturation/activation status. Immature DCs have the ability to generate regulatory T cells while mature/activated DCs express high levels of the major histocompatibility complex molecules together with co-stimulatory signals that drive T cells towards an inflammatory profile: Th1 and Th17. It was observed that autoimmune disease patients present altered dendritic cells both in frequency and in function. Thus, the modulation of DCs might become an interesting strategy to reduce the exacerbated inflammation. In this field of investigation, several drugs such as dexamethasone have been employed with relatively success. Recently, our group have demonstrated that the administration of chloroquine reduces the severity of Experimental Autoimmune Encephalomyelitis (EAE) through the expansion of regulatory T cells. The chronic consumption of chloroquine leads to toxic effects, therefore, we also demonstrated that chloroquine modulates DCs, inducing an immature profile in these cells, and when adoptively transferred to EAE-inflicted mice, the clinical score of the disease is reduced, although the precise mechanism is still unknown. Preliminary experiments conducted in our lab suggest that nitric oxide may play a role in the suppressive ability of chloroquine-modulated DCs. In this context, the aim of the present study is to evaluate the role of nitric oxide in the modulation of bone marrow-derived dendritic cells and in the generation of regulatory T cells in vitro.