Cellular and molecular mechanisms underlying systemic autoimmune and inflammatory disorders

Abstract

Lupus disease, a prototype of autoimmune and rheumatic disorders, is intriguing clinically and immunologically for its systemic nature and complexity in the pathogenesis. The initiation and perpetuation of a chronic inflammatory cascade are believed to result in multiple tissue and organ damages, but the underlying mechanisms for such a systemic loss of tolerance are still to be understood. Our studies have been focused on the roles, abnormalities, disease association and causal relationship of dendritic cells (DC), regulatory T (Treg) and B (Breg) cells in systemic autoimmunity. We showed how defects in the induction and peripheral expansion of these regulatory cells could be implicated in lupus and related inflammatory disorders. Different cytokines (IL-2, IL-10, IL-15, IL-33, IL-35) were found to be critically involved in the very processes that controlled the regulator versus effector cell expansion and functions. The therapeutic potential, as well as complications, of using these regulatory cells and molecules for treating autoimmune diseases are also discussed.