Session Title: Rheumatoid Arthritis: Animal Models
Session Type: Abstract Submissions (ACR)
Rheumatoid arthritis (RA) is an autoimmune disease that leads to destruction of joints. Although etiology of RA is unknown, both genetic and environmental factors are involved in predisposition to develop RA. Genome wide association studies have shown that among the genetic factors, the strongest association of RA is with MHC region, the most significant being HLA-DRB1*0401 and DQ8. A recent study showed that patients with RA have an imbalance of gut microbiota suggesting its role in regulation of this disease. Analysis of fecal microbiota of patients with RA showed significantly less Bifidobacteria and bacteria of the Bacteroides-Porphyromonas-Prevotella group, and the E. rectale – C. coccoides group than the fecal microbiota of patients with non-inflammatory Fibromyalgia. Since these bacterial species are known to belong to the most common genera and groups in the human fecal microbiota, their absence in RA patients might suggest a protective role of these commensal bacteria in RA.
We have generated a mouse model of rheumatoid arthritis using HLA transgenic mice expressing RA-susceptible gene, HLA-DQ8 in the absence of their endogenous class II genes. Recently, we isolated Prevotella histicola, anaerobic commensal bacteria of Human gut, from bowel of a patient and have shown that it possesses anti-inflammatory activity.
In this study we have tested our hypothesis if systemic disease like RA can be modulated via gut. HLA-DQ8 transgenic mice develop collagen-induced arthritis (CIA) following immunization with type II collagen (CII). We have used these transgenic mice to test if gut-derived commensal bacteria can regulate immune response and modulate arthritis. Treatment with P. histicola did not lead to any pathology in the gut. Transgenic mice immunized with CII and treated with P. histicola showed suppression of antigen-specific cellular immune response with a significant reduced production of inflammatory cytokines. Treatment with P. histicola led to generation of T regulatory cells in the gut and increased production of IL-10 in treated group compared to controls. Treatment of mice induced for arthritis in a therapeutic protocol led to a significant decrease in incidence (40% in treated versus 80% of control) and severity of arthritis.
P. histicola modulated immune responses in the gut thereby modulating systemic immune response and suppression of arthritis suggesting this treatment can induce tolerance in periphery leading to systemic immune suppression. Since bacteria being used for treatment is a gut-derived commensal, there are less likely to be significant side effects.
H. S. Luthra,
J. A. Murray,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/commensal-gut-derived-bacteria-as-therapy-for-systemic-autoimmune-disease/