A recent review of the epidemiologic evidence of environmental factors in human autoimmune diseases concluded that exposure to crystalline silica contributes to the development of a number of autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), and antineutrophil cytoplasmic antibody (ANCA)-related vasculitis ( 5). These factors include the food we eat, the fluids we drink, the air we breathe, chemicals (natural and synthetic), infections, by-products of manufacturing processes, and radiation ( 2– 4). However, numerous questions remain unanswered.Įnvironmental factors play a significant role in the development of human autoimmunity ( 1). The variable frequency of these immunological features following silica exposure suggests substantial genetic involvement and gene/environment interaction in silica-induced autoimmunity. Nonetheless, the findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, and autoantibodies and tissue damage. Significantly, it is unclear whether silica-induced inflammation and fibrosis contribute similarly to the development of autoimmunity. The steps in the development of silicosis, including acute and chronic inflammation and fibrosis, have different molecular and cellular requirements, suggesting that silica-induced inflammation and fibrosis may be mechanistically separate. Silica particles are encased by collagen leading to fibrosis and the nodular lesions characteristic of the disease. Ingestion of these particles by macrophages initiates an inflammatory response, which stimulates fibroblasts to proliferate and produce collagen. The pathophysiology of silicosis consists of deposition of silica particles in the alveoli of the lung. Although little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease, there is a voluminous literature on silica exposure and silicosis that may help identify immune processes that precede development of autoimmunity. Evidence for the link with autoimmune disease comes from epidemiological studies linking occupational exposure to crystalline silica dust with the systemic autoimmune diseases systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Inhalation of dust containing crystalline silica is associated with a number of acute and chronic diseases including systemic autoimmune diseases. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.
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