Cigarette smoke induces immune responses to vimentin in both, arthritis-susceptible and -resistant humanized Mice

Mitali Bidkar, Robert Vassallo, David Luckey, Michele Smart, Kelly Mouapi, Veena Taneja

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease marked by chronic synovial inflammation and both, genetic and environmental factors are involved in its pathogenesis. Human leukocyte antigen (HLA) DRB1∗0401 is associated with susceptibility to develop RA, while cigarette smoke (CS) exposure promotes seropositive disease with increased severity in DRB1∗0401+ individuals. Smokers have higher levels of antibodies against citrullinated peptides. In this study, we determined whether the response to a known autoantigen, Vimentin (Vim) is shared epitope specific and how CS influences this response using transgenic-mice carrying RA-susceptible,∗0401, and -resistant, ∗0402, genes. Following relatively brief exposure to CS, peptidyl arginine deiminase (PAD) enzyme expression was increased in murine lungs. Cigarette smoking led to production of Interferon (IFN)-ã with reduced levels of Interleukin (IL)-10 by splenocytes of ∗0401 mice. In contrast, CS augmented Th2 cytokines along with T-regulatory cells in ∗0402 mice. An increase in levels of antibodies to native and citrullinated Vim was observed in naïve mice of both strains following CS exposure. Our data showed that both arthritis-susceptible and -resistant mice can generate cellular and humoral immunity to Vim; however CSinduced modulation of host immunity is dependent on the interaction with the host HLA genes.

Original languageEnglish (US)
Article numbere0162341
JournalPloS one
Volume11
Issue number9
DOIs
StatePublished - Sep 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'Cigarette smoke induces immune responses to vimentin in both, arthritis-susceptible and -resistant humanized Mice'. Together they form a unique fingerprint.

Cite this