Dendritic Cells: The Orchestrators of the Inflammatory Response in Autoimmune Diseases

Autoimmune diseases are characterized by qualitative and quantitative abnormalities in multiple components of innate and adaptive immunity. Among the cells of the immune system involved in the pathogenic autoimmune response, dendritic cells (DCs) are essential in the initiation and perpetuation of inflammation. Through their pattern recognition receptors, DCs become active when they detect pathogens and signs of tissue damage. Multiple studies have shown the presence of DCs in inflamed tissues of patients with autoimmune diseases and in most cases they show an activated phenotype. In addition, in subjects with autoimmune diseases, nonimmune cells synthesize chemokines that attract DCs, which capture antigens from the environment, present them to T lymphocytes, and secrete cytokines that polarize the cooperative immune response toward Th1 and Th17 that have been shown to be important in multiple autoimmune diseases. In addition, plasmacytoid DCs are professional producers of IFN-α. This cytokine induces the maturation of conventional DCs and promotes T CD4+-independent isotype change and autoantibodies production by B cells. Finally, because DCs participate in the pathophysiology of virtually all autoimmune diseases, it is natural to think that the use of tolerogenic DCs to recover the antigen-specific peripheral tolerance is a plausible therapeutic strategy in the future. Tolerogenic DCs have been tested in animal models of autoimmunity and they offer the hope to be an effective treatment for autoimmune diseases without the need to occupy systemic immunosuppressive therapies.