CD40 is functionally expressed on human keratinocytes

Eur J Immunol. 1996 Oct;26(10):2329-34. doi: 10.1002/eji.1830261009.


The CD40/gp39 pathway is known to be an important feature of B/T cell collaboration leading to T cell-dependent activation, proliferation or differentiation of B cells. Additionally, CD40 is involved in the regulation of B cell survival and apoptosis. Recently, CD40 has been shown to be expressed functionally on non-hematopoietic cells, i.e. endothelial cells. Here, we demonstrate that human keratinocytes (KC) cultured in vitro express CD40 constitutively. The surface expression of CD40 is markedly up-regulated following stimulation with interferon (IFN)-gamma, but not with tumor necrosis factor-alpha or interleukin (IL)-1 beta. This process is regulated at the CD40 mRNA level as demonstrated by Northern blot analysis. Furthermore, ligation of CD40 via soluble gp39, the CD40 ligand, enhances intercellular adhesion molecule (ICAM)-1 and Bcl-x up-regulation on IFN-gamma-stimulated KC, but not lymphocyte function-associated antigen (LFA)-3, B7-2, HLA-DR, or Fas expression. The release of IL-8 is also induced following CD40 ligation on KC. In psoriasis, a T cell-mediated inflammatory skin disease, KC have a markedly enhanced expression of CD40. This expression co-localizes with the expression of ICAM-1, Bcl-x, and an influx of CD3+ T cells. These findings suggest a functional role of CD40 on KC in inflammatory skin disorders such as psoriasis and could make a therapeutic intervention by disrupting the CD40/gp39 pathway an approach to consider in these inflammatory skin diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD3 Complex / metabolism
  • CD40 Antigens / genetics
  • CD40 Antigens / metabolism*
  • Cells, Cultured
  • Gene Expression
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-8 / metabolism
  • Keratinocytes / immunology*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Psoriasis / immunology
  • RNA, Messenger / genetics
  • Signal Transduction
  • Skin Diseases / immunology
  • bcl-X Protein


  • BCL2L1 protein, human
  • CD3 Complex
  • CD40 Antigens
  • Interleukin-8
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-X Protein
  • Intercellular Adhesion Molecule-1