The involvement of epithelial Fas in a human model of graft versus host disease

Transplantation. 2011 May 15;91(9):946-51. doi: 10.1097/TP.0b013e318212c833.


Background: Graft-versus-host disease (GVHD) is an important complication occurring after hematopoietic stem-cell transplantation (HSCT). Animal model studies have shown the involvement of the Fas (APO-1/CD95)/Fas-Ligand pathway in GVHD pathogenesis, but its association with cutaneous GVHD in human remains to be established.

Methods: In the present study, Fas involvement in skin damage was assessed using a human skin explant model of GVHD. Fas and FasL expression were measured by immunohistochemistry and blockade of Fas pathway was investigated using an antagonistic anti-human Fas monoclonal antibody. In addition, levels of soluble Fas (sFas) were determined in the serum of patients receiving allogeneic HSCT with and without GVHD.

Results: The results showed that Fas up-regulation in the epithelium of human skin explants correlated with graft-versus-host reaction (GVHR) in the skin explant model (P<0.001). Decreased GVHR grades were observed by using a Fas blocking monoclonal antibody. Levels of sFas were increased post-HSCT (P<0.001) but rather than being associated with the severity of GVHD, sFas levels differed with the conditioning treatments the patients received before the HSCT.

Conclusions: Higher GVHR grades were associated with increased Fas expression in the epithelium of the skin explants. In addition, by blocking Fas-mediated apoptosis, the GVHR grades were decreased. Our study thus shows the involvement of Fas in cutaneous GVHD damage, and supports the potential use of Fas as a therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fas Ligand Protein / blood
  • Fas Ligand Protein / immunology
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / pathology
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Male
  • Skin / immunology*
  • Skin / pathology
  • Transplantation, Homologous
  • Up-Regulation
  • fas Receptor / blood
  • fas Receptor / immunology*


  • FAS protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • fas Receptor