Environmental xenobiotic exposure and autoimmunity

Susceptibility to autoimmune diseases is dependent on multigenic inheritance, environmental factors, and stochastic events. Although there has been substantial progress in identifying predisposing genetic variants, a significant challenge facing autoimmune disease research is the identification of the specific events that trigger loss of tolerance, autoreactivity and ultimately autoimmune disease. Accordingly, studies have indicated that a wide range of extrinsic factors including drugs, chemicals, microbes, and other environmental factors can induce autoimmunity, particularly systemic autoimmune diseases such as lupus. This review describes a class of environmental factors, namely xenobiotics, epidemiologically linked to human autoimmunity. Mechanisms of xenobiotic autoimmune disease induction are discussed in terms of human and animal model studies with a focus on the role of inflammation and the innate immune response. We argue that localized tissue damage and chronic inflammation elicited by xenobiotic exposure leads to the release of self-antigens and damage-associated molecular patterns as well as the appearance of ectopic lymphoid structures and secondary lymphoid hypertrophy, which provide a milieu for the production of autoreactive B and T cells that contribute to the development and persistence of autoimmunity in predisposed individuals. •Extrinsic factors, such as xenobiotics, can induce systemic autoimmunity.•Xenobiotic autoimmunity can arise de novo, or in concert with idiopathic autoimmunity.•Xenobiotic-induced chronic inflammation promotes appearance of lymphoid structures crucial to development of autoimmunity.•Studies should focus on identifying xenobiotic-induced autoimmunity in humans and development of valid experimental models.•Databases of clinical and laboratory features are needed to identify criteria for diagnosing xenobiotic-induced autoimmunity.