Mechanisms of environmental influence on human autoimmunity: A national institute of environmental health sciences expert panel workshop

Carlo Selmi, Patrick S Leung, David H. Sherr, Marilyn Diaz, Jennifer F. Nyland, Marc Monestier, Noel R. Rose, M. Eric Gershwin

Research output: Contribution to journalArticle

109 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)272-284
Number of pages13
JournalJournal of Autoimmunity
Volume39
Issue number4
DOIs
StatePublished - Dec 2012

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National Institute of Environmental Health Sciences (U.S.)
Autoimmunity
Autoimmune Diseases
Education
Diseases in Twins
Molecular Mimicry
Th17 Cells
Aryl Hydrocarbon Receptors
Monozygotic Twins
Toll-Like Receptors
Genome-Wide Association Study
Autoantigens
Regulatory T-Lymphocytes
DNA Methylation
Post Translational Protein Processing
Innate Immunity
Epigenomics
Autoantibodies
Cell Differentiation
B-Lymphocytes

Keywords

  • Adjuvant
  • Antigen modification
  • Epigenetics
  • Tolerance breakdown

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Mechanisms of environmental influence on human autoimmunity : A national institute of environmental health sciences expert panel workshop. / Selmi, Carlo; Leung, Patrick S; Sherr, David H.; Diaz, Marilyn; Nyland, Jennifer F.; Monestier, Marc; Rose, Noel R.; Gershwin, M. Eric.

In: Journal of Autoimmunity, Vol. 39, No. 4, 12.2012, p. 272-284.

Research output: Contribution to journalArticle

Selmi, Carlo ; Leung, Patrick S ; Sherr, David H. ; Diaz, Marilyn ; Nyland, Jennifer F. ; Monestier, Marc ; Rose, Noel R. ; Gershwin, M. Eric. / Mechanisms of environmental influence on human autoimmunity : A national institute of environmental health sciences expert panel workshop. In: Journal of Autoimmunity. 2012 ; Vol. 39, No. 4. pp. 272-284.
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