Microbiota modify inflammatory arthritis through mucosal inflammation and autoantibody generation
| Autor: | Kristi Kuhn, Widian K. Jubair, Jason D. Hendrickson, Sumitra Adhikari, Diana Ir, Charles E Robertson, Daniel N Frank, Nirmal K. Banda |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 198:55.16-55.16 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.198.supp.55.16 |
| Popis: | Mucosal dysbiosis occurs in patients with rheumatoid arthritis (RA), but its role in disease pathophysiology has not been well defined. Using the collagen-induced arthritis (CIA) murine model, we investigated the importance of microbiota in developing inflammatory arthritis. Dysbiosis in CIA occurred in two phases, at 14 days and 35 days after the initial immunization of bovine type II collagen (CII) in complete Freund’s adjuvant. In parallel, mucosal barrier impairment was observed with an initial insult observed at day 14 that stabilized through day 21 but worsened by day 35. Mucsoal inflammation also was observed as determined by colon histology and elevation of tissue cytokines IL-17A and IL-22. Depletion of microbiota through administration of broad-spectrum antibiotics resulted in decreased disease severity and mucosal inflammation. Unexpectedly, we observed that microbial depletion during the late, effector phase of CIA, resulted in more profound suppression of disease. Both disease severity and serum anti-CII autoantibodies correlated with microbial load, further supporting the role of microbiota driving the disease process. Finally, we confirmed that in CIA, the presence of an intact microbiota associated with the presence of RA-relevant anti-citrullinated protein antibodies, possibly through dysbiosis-stimulated activation of the host’s peptidyl arginine deiminase 4 enzyme. Clearly additional studies are needed to solidify the role of the microbiota in driving CIA, but our data together with those of others’ supports a model in which intestinal dysbiosis triggers mucosal immune responses that stimulate T and B cell activities that lead to inflammatory arthritis. |
| Databáze: | OpenAIRE |
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