Cutting Edge: Chemokine receptor CCR4 is necessary for antigen-driven cutaneous accumulation of CD4 T cells under physiological conditions.
Dual expression of chemokine receptor CCR4 and E-selectin ligand is characteristic of skin-tropic CD4 T cells from blood, lymphoid organs, and the skin itself. A strong and specific correlation exists among CCR4, its ligand CCL17/TARC, and the cutaneous lymphocyte-homing process. Nevertheless, whether CCR4 function is required for skin-specific trafficking remains an open question, which we address in this study. We developed an Ag-specific, TCR-transgenic, murine CD4 T cell adoptive transfer model that induces a mixed Th1 and Th17 cutaneous response. Within the hosts, both CCR4(+/+) and CCR4(-/-) donor CD4 T cells contribute equally well to the circulating E-selectin ligand(+) pool in response to Ag. However, only CCR4(+/+) donor cells accumulate efficiently within the skin. CCR4(-/-) cells home normally to the peritoneum, showing that they do not have a general defect in lymphocyte trafficking. We conclude that under physiological conditions, CCR4 is a nonredundant, necessary component of skin-specific lymphocyte trafficking.
Campbell
James J
JJ
Department of Dermatology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA. jcampbell@rics.bwh.harvard.edu
O'Connell
Daniel J
DJ
Wurbel
Marc-André
MA
D000818:Animals; D000941:Antigens / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000276:immunology; D019040:E-Selectin / Q000276:immunology; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010529:Peritoneal Cavity; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000172:deficiency / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D000941:Antigens; C499538:Ccl17 protein, mouse; C515355:Ccr4 protein, mouse; D054414:Chemokine CCL17; D019742:Chemokines, CC; D019040:E-Selectin; D008024:Ligands; D054398:Receptors, CCR4; D019707:Receptors, Chemokine