title: The Fas/Fas ligand apoptosis pathway underlies immunomodulatory properties of human biliary tree stem/progenitor cells.
abstract: OBJECTIVE
  Human biliary tree stem/progenitor cells (hBTSCs) are multipotent epithelial stem cells, easily obtained from the biliary tree, with the potential for regenerative medicine in liver, biliary tree, and pancreas diseases. Recent reports indicate that human mesenchymal stem cells are able to modulate the T cell immune response. However, no information exists on the capabilities of hBTSCs to control the allogeneic response. The aims of this study were to evaluate FasL expression in hBTSCs, to study the in vitro interaction between hBTSCs and human lymphocytes, and the role of Fas/FasL modulation in inducing T cell apoptosis in hBTSCs/T cell co-cultures.
  
  
  METHODS
  Fas and FasL expression were evaluated in situ and in vitro by immunofluorescence and western blotting. Co-cultures of hBTSCs with human leukocytes were used to analyze the influence of hBTSCs on lymphocytes activation and apoptosis.
  
  
  RESULTS
  hBTSCs expressed HLA antigens and FasL in situ and in vitro. Western blot data demonstrated that hBTSCs constitutively expressed high levels of FasL that increased after co-culture with T cells. Confocal microscopy demonstrated that FasL expression was restricted to EpCAM(+)/LGR5(+) cells. FACS analysis of T cells co-cultured with hBTSCs indicated that hBTSCs were able to induce apoptosis in activated CD4(+) and CD8(+) T cell populations. Moreover, the Fas receptor appears to be more expressed in T cells co-cultured with hBTSCs than in resting T cells.
  
  
  CONCLUSIONS
  Our data suggest that hBTSCs could modulate the T cell response through the production of FasL, which influences the lymphocyte Fas/FasL pathway by inducing "premature" apoptosis in CD4(+) and CD8(+) T cells.
authors: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Massimo
authors: M
authors: Riccio
authors: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Gianluca
authors: G
authors: Carnevale
authors: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Rome, Italy.
authors: Vincenzo
authors: V
authors: Cardinale
authors: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Lara
authors: L
authors: Gibellini
authors: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Sara
authors: S
authors: De Biasi
authors: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Alessandra
authors: A
authors: Pisciotta
authors: Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", Rome, Italy.
authors: Guido
authors: G
authors: Carpino
authors: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Rome, Italy.
authors: Raffaele
authors: R
authors: Gentile
authors: Department of General Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy.
authors: Pasquale B
authors: PB
authors: Berloco
authors: Department of Obstetrics and Gynecology, Sapienza University of Rome, Rome, Italy.
authors: Roberto
authors: R
authors: Brunelli
authors: Department of Obstetrics and Gynecology, Sapienza University of Rome, Rome, Italy.
authors: Carlo
authors: C
authors: Bastianelli
authors: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors: Chiara
authors: C
authors: Napoletano
authors: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors: Alfredo
authors: A
authors: Cantafora
authors: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Andrea
authors: A
authors: Cossarizza
authors: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
authors: Eugenio
authors: E
authors: Gaudio
authors: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Rome, Italy; Fondazione Eleonora Lorillard Spencer Cenci, Rome, Italy. Electronic address: domenico.alvaro@uniroma1.it.
authors: Domenico
authors: D
authors: Alvaro
authors: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Anto
authors: A
authors: De Pol
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D001659:Biliary Tract / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018920:Coculture Techniques; D053222:Fas Ligand Protein / Q000378:metabolism*; D053686:Fetal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D008213:Lymphocyte Activation; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor
keywords: Endodermal stem cells; FasL; Human biliary tree stem/progenitor cells (hBTSCs); Immune modulation; T cell apoptosis