CC chemokine receptor (CCR)4 and the CCR10 ligand cutaneous T cell-attracting chemokine (CTACK) in lymphocyte trafficking to inflamed skin.
The chemokine thymus and activation-regulated chemokine (TARC; CCL17) is displayed by cutaneous (but not intestinal) venules, and is thought to trigger vascular arrest of circulating skin homing memory T cells, which uniformly express the TARC receptor CC chemokine receptor (CCR)4. Cutaneous T cell-attracting chemokine (CTACK; CCL27), expressed by skin keratinocytes, also attracts cutaneous memory T cells, and is hypothesized to assist in lymphocyte recruitment to skin as well. Here we show that chronic cutaneous inflammation induces CD4 T cells expressing E-selectin binding activity (a marker of skin homing memory cells) in draining lymph node, and that these E-selectin ligand+ T cells migrate efficiently to TARC and to CTACK. In 24 h in vivo homing assays, stimulated lymph node T cells from wild-type mice or, surprisingly, from CCR4-deficient donors migrate efficiently to inflamed skin; and an inhibitory anti-CTACK antibody has no effect on wild-type lymphocyte recruitment. However, inhibition with anti-CTACK monoclonal antibody abrogates skin recruitment of CCR4-deficient T cells. We conclude that CTACK and CCR4 can both support homing of T cells to skin, and that either one or the other is required for lymphocyte recruitment in cutaneous delayed type hypersensitivity.
Reiss
Y
Y
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Proudfoot
A E
AE
Power
C A
CA
Campbell
J J
JJ
Butcher
E C
EC
D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000502:physiology*; D003872:Dermatitis / Q000276:immunology*; D005260:Female; D008024:Ligands; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D054447:Receptors, CCR10; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000378:metabolism* / Q000502:physiology*; D000097628:Chemokine Receptor D6
D054414:Chemokine CCL17; D019742:Chemokines, CC; D008024:Ligands; D054447:Receptors, CCR10; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; C515710:Ackr2 protein, rat; D000097628:Chemokine Receptor D6; C499538:Ccl17 protein, mouse; C515707:Ccr10 protein, mouse; C515355:Ccr4 protein, mouse; C515356:Ccr4 protein, rat