Cellular and humoral immunity in arthritis are profoundly influenced by the interaction between cigarette smoke effects and host HLA-DR and DQ genes

Robert Vassallo, David Luckey, Marshall Behrens, Benjamin Madden, Harvinder Luthra, Chella David, Veena Taneja

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Individuals carrying DRB1*0401 who smoke cigarettes are at an increased risk of developing severe seropositive RA. To determine how cigarette smoke (CS) interacts with host genetic factors in the induction of RA-associated autoimmunity, we used transgenic mice carrying the RA-susceptible HLA genes DR4 and DQ8, but lacking all endogenous murine class II molecules. Cigarette smoke exposure augmented peptidylarginine deiminase (PAD) enzyme expression, and enhanced immune responses to citrullinated collagen and vimentin. Here we show for the first time that DQ molecules can present citrullinated peptides much more efficiently than native peptides. Interestingly, CS exposure suppressed collagen-induced arthritis (CIA) in DRB1*0401 mice although innate immune response was enhanced. On the other hand, CS exposure exacerbated CIA in DQ8 mice, which was accompanied by an increased expression of Th17 gene transcripts in lungs. These observations suggest that cigarette smoke promotes antigen-specific autoimmunity that is profoundly influenced by host genetic factors.

Original languageEnglish (US)
Pages (from-to)25-35
Number of pages11
JournalClinical Immunology
Volume152
Issue number1-2
DOIs
StatePublished - May 2014

Keywords

  • Citrullination
  • HLA transgenic mice
  • Innate immune response
  • Rheumatoid arthritis
  • Smoking

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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