Silicosis and Silica-Induced Autoimmunity in the Diversity Outbred Mouse

Frontiers in Immunology
Jessica M MayeuxKenneth Michael Pollard

Abstract

Epidemiological studies have confidently linked occupational crystalline silica exposure to autoimmunity, but pathogenic mechanisms and role of genetic predisposition remain poorly defined. Although studies of single inbred strains have yielded insights, understanding the relationships between lung pathology, silica-induced autoimmunity, and genetic predisposition will require examination of a broad spectrum of responses and susceptibilities. We defined the characteristics of silicosis and autoimmunity and their relationships using the genetically heterogeneous diversity outbred (DO) mouse population and determined the suitability of this model for investigating silica-induced autoimmunity. Clinically relevant lung and autoimmune phenotypes were assessed 12 weeks after a transoral dose of 0, 5, or 10 mg crystalline silica in large cohorts of DO mice. Data were further analyzed for correlations, hierarchical clustering, and sex effects. DO mice exhibited a wide range of responses to silica, including mild to severe silicosis and importantly silica-induced systemic autoimmunity. Strikingly, about half of PBS controls were anti-nuclear antibodies (ANA) positive, however, few had disease-associated specificities, whereas most ANAs ...Continue Reading

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Citations

Oct 1, 2019·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Jessica L RayAndrij Holian
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Methods Mentioned

BETA
bronchoalveolar lavage
ELISAs
ELISA
Protein Assay
lavage

Software Mentioned

TreeView
Leica Application Suite AF
GraphPad
Cluster
Digital Image Hub

Related Concepts

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