Possible involvement of CD14+ CD16+ monocyte lineage cells in the epidermal damage of Stevens-Johnson syndrome and toxic epidermal necrolysis

Br J Dermatol. 2012 Feb;166(2):322-30. doi: 10.1111/j.1365-2133.2011.10649.x. Epub 2011 Dec 5.

Abstract

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are characterized by keratinocyte apoptosis and necrosis, resulting in epidermal detachment. Although monocytes abundantly infiltrate the epidermis in SJS/TEN skin lesions, the properties and functions of these cells have not been fully examined.

Objectives: To determine the properties of monocytes infiltrating into the epidermis in SJS/TEN.

Methods: Immunostaining of skin sections was performed to examine the membrane markers of monocytes infiltrating into skin lesions.

Results: Immunostaining of cryosections from 11 SJS/TEN skin lesions revealed numerous CD14+ monocytes located along the dermoepidermal junction and throughout the epidermis. The cells coexpressed CD16, CD11c and HLA-DR. CD14+ CD16+ cells were identified in very early lesions without epidermal damage, suggesting that their infiltration is a cause, rather than a result, of epidermal damage. Moreover, these cells expressed CD80, CD86 and CD137 ligand, indicative of their ability to facilitate the proliferation and cytotoxicity of CD8+ T cells. CD16+ cells infiltrating the epidermis and detected at the dermoepidermal junction were immunostained and counted in paraffin-embedded skin sections obtained from 47 patients with drug rash manifested as TEN, SJS, maculopapular-type rash or erythema multiform-type rash. The number of CD16+ monocytes infiltrating the epidermis increased significantly, depending on the grade of epidermal damage.

Conclusions: These findings suggest that the appearance of CD14+ CD16+ cells of monocyte lineage plays an important role in the epidermal damage associated with SJS/TEN, most probably by enhancing the cytotoxicity of CD8+ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-1BB Ligand / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / physiology
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / metabolism
  • Cell Lineage
  • Cell Proliferation
  • Epidermis / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Keratinocytes / pathology
  • Lipopolysaccharide Receptors / metabolism*
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Receptors, IgG / metabolism*
  • Stevens-Johnson Syndrome / immunology
  • Stevens-Johnson Syndrome / pathology*

Substances

  • 4-1BB Ligand
  • B7-1 Antigen
  • B7-2 Antigen
  • Lipopolysaccharide Receptors
  • Receptors, IgG
  • TNFSF9 protein, human