Marshall, Behrens D

HLA‐DQ8 is associated with certain autoimmune diseases including celiac disease, juvenile diabetes mellitus, and rheumatoid arthritis. These diseases have significantly high morbidity and mortality rates and often require chronic, life‐long immunosuppressive therapy, especially in the case of rheumatoid arthritis. Recent studies have determined that commensal microorganisms from the gut flora can modulate the development of autoimmune diseases although the mechanism of action remains elusive. We examined the systemic immunological effects following oral exposure to live commensal bacteria within naive AEoDQ8 mice. Specifically, Prevotella species was isolated and cultured from the small intestine of celiac patients and administered by oral gavages every 48 hours for 2 weeks to AEo DQ8 mice. Significant decreases in serum IL‐17 expressed in pg/ml (2406 to 1662, □33%) and GM‐CSF (15.5 to 9.7, □40%) were detected in the sera of the group administered live bacteria as compared to the group administered sham gavages. The decrease in serum IL‐6, G‐CSF, MIP1a, and MIP1b levels did not reach statistical significance. Also, no difference in serum TGFbeta levels was observed between the two groups. However, FACS analysis revealed an increase in splenic CD4+CD25+FoxP3+ regulatory T‐cells in the group administered live bacteria as compared to the control group, 11.4% vs. 8.0%, respectively. These findings suggest that gram negative, commensal bacteria can suppress the expression of pro‐inflammatory IL‐17 at a systemic level.