Silicosis and silica-induced autoimmunity in multiple Collaborative Cross strains
Abstract Background: The connection between pulmonary silica dust exposure and the development of systemic autoimmunity is well established. However, the extent to which genetic differences influence the severity of silica-induced autoimmunity remains unclear. Objective: Investigate the role of sili...
Saved in:
Published in | The Journal of immunology (1950) Vol. 212; no. 1_Supplement; pp. 787 - 787_7461 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
01.05.2024
|
Online Access | Get full text |
Cover
Loading…
Summary: | Abstract Background: The connection between pulmonary silica dust exposure and the development of systemic autoimmunity is well established. However, the extent to which genetic differences influence the severity of silica-induced autoimmunity remains unclear. Objective: Investigate the role of silica exposure on disease biomarkers (cytokines/chemokines and antinuclear antibodies (ANA)) and systemic autoimmune disease in genetically diverse Collaborative Cross recombinant inbred (CC RI) mice. Methods: Baseline serum ANA and chemokines/cytokines were assessed from 61 CC RI strains. Six CC RI strains, chosen to represent different baseline immune phenotypes, were exposed to 5 mg crystalline silica or PBS and examined 12 weeks later for serum ANA, bronchoalveolar lavage fluid cell counts, tracheobronchial lymph node and spleen weights, and histological assessment of silicosis and lupus nephritis. Results: All strains developed silicosis; however, two strains with low baseline immune activity did not develop silica-induced autoimmunity. In contrast, strains with higher baseline immune activity developed elevated ANA levels with strain variation in ANA types. One strain developed lupus nephritis, with significantly greater severity compared to controls. Conclusion: Baseline immune activity significantly influences the development of silica-induced autoimmunity and lung inflammation; however, genetics may be mediating silicosis and systemic autoimmunity independently. |
---|---|
ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.212.supp.0787.7461 |