Commensal Gut Derived Anaerobes as Novel Therapy for Inflammatory Autoimmune Diseases.

摘要

Rheumatoid arthritis (RA) and multiple sclerosis (MS) are chronic inflammatory autoimmune diseases affecting millions of people. Here we are proposing a novel approach to cure MS, by administration of a specific strain of human commensal bacteria. Recent studies have shown that intestinal microflora plays an important role in the health of the host and posses probiotics like qualities. We hypothesize that Gram-negative commensal bacteria from human gut have the potential to be used as a therapeutic agent. We have used collagen induced arthritis (CIA) in HLA-DR4DQ8 mice and PLP91-110 induced experimental autoimmune encephalomyelitis (EAE) HLA-DR3DQ8 mice to test our hypothesis that treatment with commensal bacteria Prevotella histicola can modulate disease. First using various doses of bacteria, we have identified the optimal dose to be used for treatment of CIA as well as EAE. Our in vitro and in vivo data showing suppression of antigen-specific immune response in EAE and arthritis in P. histicola treated mice suggest generation of peripheral tolerance via gut. Our studies show that treatment with P histicola suppresses arthritis/EAE via gut and generation of regulatory DCs and T regulatory cells. Our data indicates that P histicola induced immune responses in the gut cause induction of immune tolerance in periphery leading to suppression of antigen specific response.