Although most autoimmune diseases develop without a manifest cause, epidemiological studies indicate that external factors play an important role in triggering or aggravating autoimmune processes in genetically predisposed individuals. Nevertheless, most autoimmune disease-promoting environmental agents are unknown because their relationships to immune function are not understood. Thus, the study of animal models of chemically-induced autoimmunity should shed light on the pathways involved and allow us to identify these agents. The rodent model of heavy metal-induced autoimmunity is one of the most intriguing experimental systems available to address such questions. Although the ultimate pathophysiology of this model remains mysterious, recent studies have started to elucidate the mechanisms by which heavy metal exposure leads to immune activation and loss of self-tolerance.
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