Difference in Th1 and Th17 lymphocyte adhesion to endothelium.
T cell subset-specific migration to inflammatory sites is tightly regulated and involves interaction of the T cells with the endothelium. Th17 cells often appear at different inflammatory sites than Th1 cells, or both subsets appear at the same sites but at different times. Differences in T cell subset adhesion to endothelium may contribute to subset-specific migratory behavior, but this possibility has not been well studied. We examined the adhesion of mouse Th17 cells to endothelial adhesion molecules and endothelium under flow in vitro and to microvessels in vivo and we characterized their migratory phenotype by flow cytometry and quantitative RT-PCR. More Th17 than Th1 cells interacted with E-selectin. Fewer Th17 than Th1 cells bound to TNF-α-activated E-selectin-deficient endothelial cells, and intravital microscopy studies demonstrated that Th17 cells engage in more rolling interactions with TNF-α-treated microvessels than Th1 cells in wild-type mice but not in E-selectin-deficient mice. Th17 adhesion to ICAM-1 was dependent on integrin activation by CCL20, the ligand for CCR6, which is highly expressed by Th17 cells. In an air pouch model of inflammation, CCL20 triggered recruitment of Th17 but not Th1 cells. These data provide evidence that E-selectin- and ICAM-1-dependent adhesion of Th17 and Th1 cells with endothelium are quantitatively different.
Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Pilar
P
Alcaide
Elena
E
Maganto-Garcia
Gail
G
Newton
Richard
R
Travers
Kevin J
KJ
Croce
De-xiu
DX
Bu
Francis W
FW
Luscinskas
Andrew H
AH
Lichtman
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology*; D054418:Chemokine CCL20 / Q000378:metabolism; D019040:E-Selectin / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D051379:Mice; D018417:Th1 Cells / Q000502:physiology*; D058504:Th17 Cells
C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; D019040:E-Selectin; D018799:Intercellular Adhesion Molecule-1