title: The involvement of epithelial Fas in a human model of graft versus host disease.
abstract: 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.
authors.affiliation: IMED AB, 171 65 Solna, Sweden.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ruffin
authors.forename: Shaheda S
authors.initials: SS
authors.lastname: Ahmed
authors.forename: Lyda M
authors.initials: LM
authors.lastname: Osorio
authors.forename: Xiao Nong
authors.initials: XN
authors.lastname: Wang
authors.forename: Graham H
authors.initials: GH
authors.lastname: Jackson
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Collin
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Ekre
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiodi
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dickinson
mesh_terms: D000818:Animals; D053222:Fas Ligand Protein / Q000097:blood / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D012867:Skin / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous; D015854:Up-Regulation; D019014:fas Receptor / Q000097:blood / Q000276:immunology*
chemical_list: C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor