O-009 Particle-Induced Autoimmune Features in C57bl/6j and Nod/Shiltj Mice

Introduction Occupational exposure to crystalline silica is associated with an elevated risk of autoimmune diseases in susceptible individuals, yet underlying mechanisms, likely influenced by gene-environment interactions, remain unclear. We aimed to investigate the immunotoxicological effects of exposure to crystalline silica considering the effect of genetic background in C57BL/6J and NOD/ShiLtJ mice. Methods C57BL/6J and NOD/ShiLtJ mice were oropharyngeally exposed to 4mg quartz (median size about 2 µm) with animal ethics committee approval of KU Leuven (P111/2021). Ten weeks post-exposure, bronchoalveolar lavage fluid (BALF), lungs and serum were collected to evaluate inflammatory cell count, lung histology, lung fibrosis and antinuclear antibody (ANA) presence. Results Silica exposed mice developed a local inflammatory response characterized by inflammatory infiltrates, recruitment of macrophages/neutrophils and mild lung fibrosis, which was more pronounced in the NOD/ShiLtJ mice. In BALF, the silica-exposed NOD/ShiLtJ mice showed significantly high ANA scores with about 40% of mice reaching a score of 3-4, while silica-exposed C57BL/6J mice had lower scores, only reaching up to 2. Silica-exposed NOD/ShiLtJ mice also developed systemic ANAs present in serum, with scores reaching up to 4, whereas silica-exposed C57BL/6J mice only reached scores up to 2-3. Discussion The autoimmune-prone background of NOD/ShiLtJ mice characterized by an H2(g7) MHC haplotype and genetic variants impacting tolerance and T cell functioning seems to render them more susceptible to an inflammatory phenotype facilitating the development of autoantibodies. Conclusion The autoimmune-prone genetic background of the NOD/ShiLtJ mice appears to be a critical factor contributing to their susceptibility to develop silica-induced features of autoimmune disease.