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

Significance: Autoimmune diseases are progressively affecting westernized societies, as the proportion of individuals suffering from autoimmunity is steadily increasing over the past decades. Understanding the role of reactive oxygen species (ROS) in modulation of the immune response in the pathogenesis of autoimmune disorders is of utmost importance. The focus of this review is the regulation of ROS production within tolerogenic dendritic cells (tolDCs) and regulatory T (Treg) cells that have the essential role in the prevention of autoimmune diseases and significant potency in their therapy. Recent Advances: It is now clear that ROS are extremely important for the proper function of both DC and T cells. Antigen processing/presentation and the ability of DC to activate T cells depend upon the ROS availability. Treg differentiation, suppressive function, and stability are profoundly influenced by ROS presence. Critical Issues: Although a plethora of results on the relation between ROS and immune cells exist, it remains unclear whether ROS modulation is a productive way for skewing T cells and DCs toward a tolerogenic phenotype. Also, the possibility of ROS modulation for enhancement of regulatory properties of DC and Treg during their preparation for use in cellular therapy has to be clarified. Future Directions: Studies of DC and T cell redox regulation should allow for the improvement of the therapy of autoimmune diseases. This could be achieved through the direct therapeutic application of ROS modulators in autoimmunity, or indirectly through ROS-dependent enhancement of tolDC and Treg preparation for cell-based immunotherapy. Antioxid. Redox Signal. 34, 364-382.