CD40 is functionally expressed on human keratinocytes

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)‐γ, but not with tumor necrosis factor‐α or interleukin (IL)‐1β. 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‐γ‐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.