Cigarette Smoke Induces Immune Responses to Vimentin in both, Arthritis-Susceptible and -Resistant Humanized Mice.
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)-γ 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 CS-induced modulation of host immunity is dependent on the interaction with the host HLA genes.
Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America.
Mitali
M
Bidkar
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
Robert
R
Vassallo
Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America.
David
D
Luckey
Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America.
Michele
M
Smart
Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America.
Kelly
K
Mouapi
Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America.|Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, United States of America.
Veena
http://orcid.org/0000-0003-2401-694X
V
Taneja
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology*; D004198:Disease Susceptibility; D000939:Epitopes / Q000276:immunology; D005260:Female; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D056724:Immunity, Humoral; D008168:Lung / Q000201:enzymology / Q000473:pathology; D018655:Lymphocyte Count; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000076342:Protein-Arginine Deiminases; D012907:Smoking / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology; D014746:Vimentin / Q000276:immunology*
D016207:Cytokines; D000939:Epitopes; D059811:HLA-DRB1 Chains; D014746:Vimentin; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases