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Curr Opin Toxicol. 2018 Aug;10:15-22. doi: 10.1016/j.cotox.2017.11.009. Epub 2017 Nov 21.

Environmental Xenobiotic Exposure and Autoimmunity.

Author information

1
Department of Molecular Medicine, MEM125, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA 92037.
2
Department of Surgery, School of Medicine, University of California, San Diego, 9500 Gilman Drive #0739, La Jolla, CA, USA 92093.
3
Department of Immunology and Microbiology, IMM310, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA 92037.

Abstract

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.

KEYWORDS:

animal model; autoimmunity; epidemiology; inflammation; xenobiotic

PMID:
29503968
PMCID:
PMC5831116
[Available on 2019-08-01]
DOI:
10.1016/j.cotox.2017.11.009

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