Email updates

Keep up to date with the latest news and content from BMC Medicine and BioMed Central.

Journal App

google play app store
Open Access Review

Requirements for innate immune pathways in environmentally induced autoimmunity

Kenneth Michael Pollard1* and Dwight H Kono2

Author Affiliations

1 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA

2 Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA

For all author emails, please log on.

BMC Medicine 2013, 11:100  doi:10.1186/1741-7015-11-100

Published: 4 April 2013

Abstract

There is substantial evidence that environmental triggers in combination with genetic and stochastic factors play an important role in spontaneous autoimmune disease. Although the specific environmental agents and how they promote autoimmunity remain largely unknown, in part because of diverse etiologies, environmentally induced autoimmune models can provide insights into potential mechanisms. Studies of idiopathic and environmentally induced systemic autoimmunity show that they are mediated by common adaptive immune response genes. By contrast, although the innate immune system is indispensable for autoimmunity, there are clear differences in the molecular and cellular innate components that mediate specific systemic autoimmune diseases, suggesting distinct autoimmune-promoting pathways. Some of these differences may be related to the bifurcation of toll-like receptor signaling that distinguishes interferon regulatory factor 7-mediated type I interferon production from nuclear factor-κB-driven proinflammatory cytokine expression. Accordingly, idiopathic and pristane-induced systemic autoimmunity require both type I interferon and proinflammatory cytokines whereas the less aggressive mercury-induced autoimmunity, although dependent on nucleic acid-binding toll-like receptors, does not require type I interferon but needs proinflammatory cytokines. Scavenger receptors and the inflammasome may contribute to silica-induced autoimmunity. Greater understanding of the innate mechanisms responsible for idiopathic and environmentally induced autoimmunity should yield new information into the processes that instigate and drive systemic autoimmunity.

Keywords:
Autoimmunity; Environment; Innate immunity; Lupus; mercury; Pristane; Silica; Type I interferon