Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity

Abstract

Significance: Autoimmune diseases are progressively affecting westernized societies, asthe proportion of individuals suffering from autoimmunity is steadily increasing over thepast decades. Understanding the role of reactive oxygen species (ROS) in modulation ofthe immune response in the pathogenesis of autoimmune disorders is of utmostimportance. The focus of this review is the regulation of ROS production within tolerogenicdendritic cells (tolDC) and regulatory T (Treg) cells that have the essential role in theprevention of autoimmune diseases and significant potency in their therapy.Recent Advances: It is now clear that ROS are extremely important for the proper functionof both DC and T cells. Antigen processing/presentation and the ability of DC to activate Tcells depend upon the ROS availability. Treg differentiation, suppressive function andstability are profoundly influenced by ROS presence.Critical Issues: Although a plethora of results on the relation between ROS and immunecells exists, it remains unclear whether ROS modulation is a productive way for skewing Tcells and DC towards a tolerogenic phenotype. Also, the possibility of ROS modulation forenhancement of regulatory properties of DC and Treg during their preparation for use incellular therapy has to be clarified.Future Directions: Studies of DC and T cell redox regulation should allow for theimprovement of the therapy of autoimmune diseases. This could be achieved through thedirect therapeutic application of ROS modulators in autoimmunity or indirectly, throughROS-dependent enhancement of tolDC and Treg preparation for cell-basedimmunotherapy.