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 di splayed by cutaneous (but not intestinal) venules, and is thought to trigge r vascular arrest of circulating skin homing memory T cells, which uniforml y 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 lymphoc yte recruitment to skin as well. Here we show that chronic cutaneous inflam mation induces CD4 T cells expressing E-selectin binding activity (a marker of skin homing memory cells) in draining lymph node, and that these E-sele ctin 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 sk in; and an inhibitory anti-CTACK antibody has no effect on wild-type lympho cyte recruitment. However, inhibition with anti-CTACK monoclonal antibody a brogates 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 o r the other is required for lymphocyte recruitment in cutaneous delayed typ e hypersensitivity.