Mucosal immune responses to microbiota in the development of autoimmune disease.

The etiology of most systemic autoimmune diseases remains unknown. There is often a preclinical period of systemic autoimmunity prior to the onset of clinically classifiable disease; established and emerging data suggest that dysregulated immune interactions with commensal microbiota may play a role in the initial generation of autoimmunity in this preclinical period. This article reviews potential mechanisms by which alterations of healthy microbiota may induce autoimmunity as well as mucosal microbial associations with autoimmune diseases. If mucosal microbiota lead to the development of autoimmunity, these mucosal sites, microorganisms, and immunologic mechanisms can be targeted to prevent the onset of systemic autoimmune disease.