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

Cellular & Molecular Immunology volume 16, pages 674–675 (2019)Cite this article

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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.

The study included anonymized healthy blood donors who reported themselves as active smokers (n = 22) and control nonsmokers (n = 36) (supplementary table 1). Informed consent was obtained from all subjects prior to blood donation by the Oslo Blood Bank according to Norwegian laws and regulations (approval 2015/1591, Norwegian South-Eastern REC). Th17 cells were cultured as described previously4 in the presence of 21 or 1% oxygen. The cytokine levels in supernatants were analyzed using a Legendplex kit (BioLegend) with a BD Fortessa flow cytometer (Oslo University Flow Cytometry Core Facility). Genotyping was performed using an SBT Resolver DRB1 kit (Conexio Genomics, Australia), and the data were analyzed with Assign Software (Conexio Genomics).

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Acknowledgements

We thank Leonid Padyukov and Lars Klareskog (Karolinska University) for their advice and Jorunn Johansen (Department of Immunology, Oslo University Hospital) for help with HLA typing. This study was supported by the University of Oslo (IMB-2016 to BS), the Norwegian Research Council (ES 572317), and the Throne Holst Foundation (THS-2016/17 to BS).

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Authors and Affiliations

  1. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

    Roman Volchenkov, Jason Matthews & Bjørn S. Skålhegg

  2. Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

    Manuela Zucknick

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  1. Roman Volchenkov
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  2. Jason Matthews
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  4. Bjørn S. Skålhegg
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Correspondence to Bjørn S. Skålhegg.

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Volchenkov, R., Matthews, J., Zucknick, M. et al. Shared epitope is associated with the reactivity of Th17 cells to cigarette smoke extract regardless of smoking history. Cell Mol Immunol 16, 674–675 (2019). https://doi.org/10.1038/s41423-019-0230-4

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