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Environmental Basis of Autoimmunity

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Abstract

The three common themes that underlie the induction and perpetuation of autoimmunity are genetic predisposition, environmental factors, and immune regulation. Environmental factors have gained much attention for their role in triggering autoimmunity, with increasing evidence of their influence as demonstrated by epidemiological studies, laboratory research, and animal studies. Environmental factors known to trigger and perpetuate autoimmunity include infections, gut microbiota, as well as physical and environmental agents. To address these issues, we will review major potential mechanisms that underlie autoimmunity including molecular mimicry, epitope spreading, bystander activation, polyclonal activation of B and T cells, infections, and autoinflammatory activation of innate immunity. The association of the gut microbiota on autoimmunity will be particularly highlighted by their interaction with pharmaceutical agents that may lead to organ-specific autoimmunity. Nonetheless, and we will emphasize this point, the precise mechanism of environmental influence on disease pathogenesis remains elusive.

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Abbreviations

AIDs:

Autoinflammatory diseases

AIH:

Autoimmune hepatitis

APCs:

Antigen-presenting cells

ASGPR:

Asialo glycoprotein receptor

DIA:

Drug-induced autoimmunity

EBV:

Epstein-Barr Virus

HAV:

Hepatitis A virus

HCV:

Hepatitis C Virus

HLA:

Human leukocyte antigen

IFN:

Interferon

IUL:

Interleukin

LSE:

Systemic lupus erythematosus

NLRs:

Nucleotide-binding oligomerization domain-like receptors

NLRC4:

NLR family CARD domain-containing protein 4

Oss:

Organic solvents

PAMPs:

Pathogen-associated molecular patterns

PBC:

Primary biliary cirrhosis

PDC:

Pyruvate dehydrogenase complex

PRRs:

Pattern recognition receptor

RA:

Rheumatoid arthritis

TACE:

TNF-a-converting enzyme

TLRs:

Toll-like receptors

TNF:

Tumor necrosis factor

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Authors and Affiliations

  1. Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

    Annarosa Floreani & Patrick S. C. Leung

  2. Division of Rheumatology, Allergy, and Clinical Immunology, University of California Davis, Davis, CA, USA

    M. Eric Gershwin

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  1. Annarosa Floreani
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Floreani, A., Leung, P.S.C. & Gershwin, M.E. Environmental Basis of Autoimmunity. Clinic Rev Allerg Immunol 50, 287–300 (2016). https://doi.org/10.1007/s12016-015-8493-8

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