title: CXCR6 regulates the recruitment of pro-inflammatory IL-17A-producing T cells into atherosclerotic aortas.
abstract: 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.
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507-1969, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Butcher
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507-1969, USA.
authors.forename: Chih-I
authors.initials: CI
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507-1969, USA.
authors.forename: Tayab
authors.initials: T
authors.lastname: Waseem
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507-1969, USA galkinev@evms.edu.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Galkina
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000276:immunology; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D000075744:Receptors, CXCR6 / Q000235:genetics / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; C482906:Cxcr6 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D000075744:Receptors, CXCR6
keywords: IL-17A; atherosclerosis; chemokine receptor; immune system; lymphocytes