A novel mouse model of silicosis and silica-induced inflammatory arthritis

• Published in: The Journal of immunology (1950) Vol. 212; no. 1_Supplement; pp. 651 - 651_7840
• Main Authors: de Ocampo, Caroline, Mayeux, Jessica, Kono, Dwight, Pollard, Michael, Janssen, Lisa
• Format: Journal Article
• Language: English
• Published: 01.05.2024
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.212.supp.0651.7840

Abstract Introduction: A strong association between silica dust exposure and development of systemic autoimmune diseases, including rheumatoid arthritis (RA), is widely recognized; however, a direct mechanism has yet to be established. To elucidate this connection, we investigated the role of pulmonary silica exposure in promoting silicosis and RA in BXD2/TyJ mice. Methods: BXD2/TyJ mice exposed to 5 mg crystalline silica or PBS and examined 1-, 2-, 6-, 12-, 20-weeks later. Total immunoglobulin-G and -M, as well as autoantibody levels, measured in serum and bronchioalveolar lavage fluid (BALF), and lung and ankle tissue assessed histologically. Immune cells characterized in lung, spleen, and tracheobronchial lymph node with flow cytometry. B and T cell-containing pulmonary lymphoid accumulations visualized with immunofluorescent staining. Results: Severe silicosis was observed, and B and T cell-containing lymphoid accumulations were detected in the lung as early as 2-weeks following silica exposure. Markedly increased levels of a range of autoantibodies were detected beginning 2-weeks after silica exposure in BALF and 6-weeks in serum. Significantly higher ankle synovitis and bone erosion was observed beginning at 12-weeks post silica exposure compared to controls. Conclusion: Silica exposure accelerates severe inflammatory arthritis in a susceptible background, establishing a model to study the connection between mucosal inflammation and rheumatoid arthritis.