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

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+TCR+ 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+TCR+ 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+TCR+ T-cell recruitment into atherosclerotic lesions.

Source: International Immunology - April 27, 2016 Category: Allergy & Immunology Authors: Butcher, M. J., Wu, C.-I., Waseem, T., Galkina, E. V. Tags: Short communication Source Type: research