Shared epitope is associated with the reactivity of Th17 cells to cigarette smoke extract regardless of smoking history

摘要

Rheumatoid arthritis(RA)severity has been linked to the combination of the HLA-DRB1 amino acid sequence motif called“shared epitope”(SE)and cigarette smoking(CS).1 Animal studies support the association of DRB1 alleles and CS with arthritis susceptibility2,3 and highlight the involvement of IL-17-producing T helper 17(Th17)cells in arthritis through the activation of aryl hydrocarbon receptor(AhR).We have previously reported4 with a limited group of donors that cigarette smoke extract(CSE)treatment of Th17 cells leads to reduced cytokine production and prevents normal differentiation of human Th17 cells.Taking into consideration the known association between smoking and genotype in RA,we performed a pilot study in which we enrolled healthy individuals who reported themselves as active smokers(supplementary table 1)and evaluated possible associations between smoking status,genetic background and Th17 cell reactivity to CSE.