title: Mechanisms of environmental influence on human autoimmunity: a National Institute of Environmental Health Sciences expert panel workshop.
abstract: The mechanisms leading to autoimmune diseases remain largely unknown despite numerous lines of experimental inquiry and epidemiological evidence. The growing number of genome-wide association studies and the largely incomplete concordance for autoimmune diseases in monozygotic twins support the role of the environment (including infectious agents and chemicals) in the breakdown of tolerance leading to autoimmunity via numerous mechanisms. The present article reviews the major theories on the mechanisms of the environmental influence on autoimmunity by addressing the different degrees of confidence that characterize our knowledge. The theories discussed herein include (i) the role of innate immunity mediated by toll-like receptors in triggering the autoimmune adaptive response characterizing the observed pathology; (ii) changes in spleen marginal zone B cells in autoantibody production with particular focus on the B10 subpopulation; (iii) Th17 cell differentiation and T regulatory cells in the aryl hydrocarbon receptor model; (iv) self antigen changes induced by chemical and infectious agents which could break tolerance by post-translational modifications and molecular mimicry; and finally (v) epigenetic changes, particularly DNA methylation, that are induced by environmental stimuli and may contribute to autoimmunity initiation. We are convinced that these working hypotheses, in most cases supported by solid evidence, should be viewed in parallel with animal models and epidemiological observations to provide a comprehensive picture of the environmental causes of autoimmune diseases.
authors: Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, USA. carlo.selmi@unimi.it
authors: Carlo
authors: C
authors: Selmi
authors: Patrick S C
authors: PS
authors: Leung
authors: David H
authors: DH
authors: Sherr
authors: Marilyn
authors: M
authors: Diaz
authors: Jennifer F
authors: JF
authors: Nyland
authors: Marc
authors: M
authors: Monestier
authors: Noel R
authors: NR
authors: Rose
authors: M Eric
authors: ME
authors: Gershwin
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics; D015551:Autoimmunity / Q000187:drug effects; D001688:Biological Products / Q000633:toxicity*; D003226:Congresses as Topic; D004785:Environmental Pollutants / Q000633:toxicity*; D044127:Epigenesis, Genetic / Q000276:immunology; D059647:Gene-Environment Interaction; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D018448:Models, Immunological; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D001688:Biological Products; D004785:Environmental Pollutants; D051193:Toll-Like Receptors