CXCR6 regulates the recruitment of pro-inflammatory IL-17A-producing T cells into atherosclerotic aortas

Int Immunol. 2016 May;28(5):255-61. doi: 10.1093/intimm/dxv068. Epub 2015 Nov 27.


The adaptive immune response is involved in the development and progression of atherosclerosis and IL-17A(+) cells play a role in this disease. Although elevated number of CD4(+) IL-17A(+) (Th17) and IL-17A(+)TCRγδ(+) T cells are found within murine atherosclerotic aortas and human plaques, the mechanisms governing IL-17A(+) T-cell migration to atherosclerotic lesions are unclear. The chemokine receptor CXCR6 is expressed on several T-cell subsets and plays a pro-atherogenic role in atherosclerosis. Here, we used CXCR6-deficient (Cxcr6 (GFP/GFP) ) apolipoprotein E-deficient (Apoe (-/-) ) mice to investigate the involvement of CXCR6 in the recruitment IL-17A(+) T cells to atherosclerotic aortas. Flow cytometric analyses revealed reductions in Th17 and IL-17A(+)TCRγδ(+) T cells within aged Cxcr6 (GFP/GFP) Apoe (-/-) aortas, in comparison with age-matched Cxcr6 (GFP/+) Apoe (-/-) aortas. Although CXCR6-sufficient IL-17A(+) T cells efficiently migrated toward CXCL16, the migration of CXCR6-deficient IL-17A(+) T cells was abolished in transwell assays. Importantly, the recruitment of Cxcr6 (GFP/GFP) Apoe (-/-) IL-17A(+) T cells into the aortas of Apoe (-/-) recipients was markedly reduced in short-term adoptive transfer experiments. Altogether these results demonstrate an important role of CXCR6 in the regulation of pathological Th17 and IL-17A(+)TCRγδ(+) T-cell recruitment into atherosclerotic lesions.

Keywords: IL-17A; atherosclerosis; chemokine receptor; immune system; lymphocytes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aorta / immunology*
  • Aorta / pathology
  • Apolipoproteins E / genetics
  • Apolipoproteins E / immunology
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology*
  • Atherosclerosis / pathology
  • Cell Movement / genetics
  • Cell Movement / immunology*
  • Disease Models, Animal
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Mice
  • Mice, Knockout
  • Receptors, CXCR6 / genetics
  • Receptors, CXCR6 / immunology*
  • Th17 Cells / immunology*
  • Th17 Cells / pathology


  • Apolipoproteins E
  • Cxcr6 protein, mouse
  • Il17a protein, mouse
  • Interleukin-17
  • Receptors, CXCR6