CCL27-CCR10 Interactions Regulate T Cell-Mediated Skin Inflammation

Nat Med. 2002 Feb;8(2):157-65. doi: 10.1038/nm0202-157.

Abstract

The skin-associated chemokine CCL27 (also called CTACK, ALP and ESkine) and its receptor CCR10 (GPR-2) mediate chemotactic responses of skin-homing T cells in vitro. Here we report that most skin-infiltrating lymphocytes in patients suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10. Epidermal basal keratinocytes produced CCL27 protein that bound to extracellular matrix, mediated adhesion and was displayed on the surface of dermal endothelial cells. Tumor necrosis factor-alpha and interleukin-1beta induced CCL27 production whereas the glucocorticosteroid clobetasol propionate suppressed it. Circulating skin-homing CLA+ T cells, dermal microvascular endothelial cells and fibroblasts expressed CCR10 on their cell surface. In vivo, intracutaneous CCL27 injection attracted lymphocytes and, conversely, neutralization of CCL27-CCR10 interactions impaired lymphocyte recruitment to the skin leading to the suppression of allergen-induced skin inflammation. Together, these findings indicate that CCL27-CCR10 interactions have a pivotal role in T cell-mediated skin inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / immunology
  • Chemokine CCL27
  • Chemokines, CC / immunology*
  • Endothelium, Vascular / immunology
  • Extracellular Matrix / immunology
  • Humans
  • Inflammation / immunology*
  • Mice
  • Microscopy, Confocal
  • Receptors, CCR10
  • Receptors, Chemokine / immunology*
  • Receptors, Lymphocyte Homing / immunology
  • Skin / immunology*
  • Skin / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology

Substances

  • CCL27 protein, human
  • CCR10 protein, human
  • Ccl27a protein, mouse
  • Ccr10 protein, mouse
  • Chemokine CCL27
  • Chemokines, CC
  • Receptors, CCR10
  • Receptors, Chemokine
  • Receptors, Lymphocyte Homing