Involvement of CCL27-CCR10 interactions in drug-induced cutaneous reactions

J Allergy Clin Immunol. 2004 Aug;114(2):335-40. doi: 10.1016/j.jaci.2004.04.034.

Abstract

Background: Drug-induced skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, are severe bullous cutaneous diseases of uncertain etiology, although cytotoxic T cells seem to be involved. Cutaneous T cell-attracting chemokine (CTACK/CCL27) is selectively expressed in skin and attracts CCR10-expressing cells. Exclusive CTACK expression by keratinocytes suggests its involvement in inflammatory skin diseases.

Objective: We addressed whether CTACK/CCL27 production by the epidermis and CCR10+ lymphocytes are involved in toxic epidermal necrolysis and Stevens-Johnson syndrome.

Methods: We measured CTACK expression by epidermal cells in 2 patients with drug-induced bullous skin reactions and compared it to lesional skin from several drug-induced exanthemas. In parallel we measured CCR10 mRNA in peripheral blood mononuclear cells from the patients during the course of the disease and in lymphocytes infiltrating the skin.

Results: CTACK expression levels in skin biopsies from the 2 patients with drug-induced bullous reactions were higher than those found in healthy subjects or in other drug-induced exanthemas. CCR10 mRNA levels were also elevated in peripheral blood lymphocytes and in lesional skin during the acute phase of the disease. Moreover, resolution was associated with a return to baseline of both CTACK and CCR10 receptor expression.

Conclusion: CTACK-CCR10 interactions may be involved in the selective recruitment to the skin of cytotoxic lymphocytes in toxic epidermal necrolysis and Stevens-Johnson syndrome, as well as in less severe drug-induced cutaneous diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chemokine CCL27
  • Chemokines, CC / biosynthesis
  • Chemokines, CC / genetics
  • Chemokines, CC / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • Receptors, CCR10
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / physiology*
  • Stevens-Johnson Syndrome / etiology*

Substances

  • CCL27 protein, human
  • CCR10 protein, human
  • Chemokine CCL27
  • Chemokines, CC
  • RNA, Messenger
  • Receptors, CCR10
  • Receptors, Chemokine