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Accession Number:
ADA561919
Title:
Commensal Gut-Derived Anaerobes as Novel Therapy for Inflammatory Autoimmune Diseases
Descriptive Note:
Annual rept. 15 Apr 2011-14 Apr 2011
Corporate Author:
MAYO CLINIC ROCHESTER MN
Report Date:
2012-05-01
Pagination or Media Count:
12.0
Abstract:
Predisposition to rheumatoid arthritis RA is associated with the presence of genetic factors, HLA class II molecules, DR4 and DQ8, being the strongest. Patients with RA show an imbalance of gut microbiota suggesting its role in regulation of disease. We have used HLA-DR4 DQ8 mice to test our hypothesis that treatment with commensal bacteria like Prevotella histicola can modulate Collagen-induced arthritis CIA. In vitro study showed that treatment of mice with P. histicola in CII-immunized mice led to suppression of antigen-specific immune response and reduction in production of inflammatory cytokines. We carried out rtPCR for various cytokines and regulatory proteins in guts of mice treated with p histicola and controls. Our data showed that treatment with p histicola led to an increase in Tregulatory protein FoxP3 as well cytokine IL-10, a cytokine produced by Treg cells and suppression of pro-inflammatory IL-23. To determine if susceptibility is associated with proinflammatory cytokines in na ve mice, we analyzed cytokines in jejenum of arthritis-susceptible 0401 and resistant 0402 mice. Our data showed that arthritis-susceptible mice had higher level of proinflammatory cytokines compared to resistant mice. These data suggest that P histicola induced immune responses in the gut can induce tolerance in periphery leading to systemic immune suppression and protection from arthritis and may be a potential target for therapy.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
