Role of nitric oxide (NO) in the modulation of experimental autoimmune encephalomyelitis (EAE) after the adoptive transfer of tolerogenic dendritic cells: influence of the MyD88-mTOR-iNOS and STAT1/3-iNOS axis

Abstract

Dendritic cells (DCs), antigen-presenting cells, are able to polarize the immune response towards an inflammatory or anti-inflammatory context depending on its maturation/activation status, leading to the generation of regulatory T cells or Th1, Th2, Th9 and Th17 profiles. Immature DCs are also called tolerogenic DCs. The modulation of DCs may be an innovative approach to control chronic inflammation, where some drugs, like dexamethasone- that has an immune-modulatory action, are being employed. Recently, our group demonstrated that chloroquine reduces the severity of Experimental Autoimmune Encephalomyelitis (EAE). Since the chronic consumption of chloroquine leads to toxic effects, we demonstrated that chloroquine is able to modulate dendritic cells towards a tolerogenic status, and upon adoptive transfer onto EAE-bearing mice disease severity was reduced by a NO-dependent mechanism. A growing body of evidences indicate that mTOR and STAT1/STAT3 signaling cascades play a role in the modulation of DCs especially in the production of nitric oxide. Therefore, the aim of this study is to evaluate the role of nitric oxide produced by chloroquine/artesunato-treated dendritic cells in the modulation of Experimental Autoimmune Encephalomyelitis. We will investigate the influence of MyD88-mTOR-iNOS and STAT1/3-iNOS axis in the modulatory function of tolerogenic dendritic cells as well. (AU)