title: Human skin-derived precursor cells are poorly immunogenic and modulate the allogeneic immune response.
abstract: Human skin-derived precursors (hSKPs) are multipotent somatic stem cells that persist within the dermis throughout adulthood and harbor potential clinical applicability. In this study, we investigated their immunogenicity and immunosuppressive features, both in vitro and in vivo. As such, this study provides a solid basis for developing their future clinical applications. We found that hSKPs express HLA-ABC molecules, but not HLA-DR, rendering them poorly immunogenic. Using a coculture set-up, we could further demonstrate that hSKPs inhibit the proliferation of allogeneic activated T cells and alter their cytokine secretion profile, in a dose-dependent manner. Cotransplantation of hSKP and human peripheral blood leukocytes (PBL) into severe combined immune-deficient mice also showed a significant impairment of the graft-versus-host response 1 week post-transplantation and a drastic increase in survival time of 60%. From a mechanistic point of view, we found that hSKPs require cell contact as well as secretion of soluble inhibitory factors in order to modulate the immune response. The expression/secretion levels of these factors further increases upon inflammation or in the presence of activated T cells. As such, we believe that these features could be beneficial in a later allogeneic clinical setting, because rejection of engrafted allogeneic hSKP might be delayed or even avoided due to their own promotion of a tolerogenic microenvironment.
authors.affiliation: Department of In Vitro Toxicology and Dermato-Cosmetology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Joery
authors.initials: J
authors.lastname: De Kock
authors.forename: Philip
authors.initials: P
authors.lastname: Meuleman
authors.forename: Gordana
authors.initials: G
authors.lastname: Raicevic
authors.forename: Robim M
authors.initials: RM
authors.lastname: Rodrigues
authors.forename: Steven
authors.initials: S
authors.lastname: Branson
authors.forename: Kesavan
authors.initials: K
authors.lastname: Meganathan
authors.forename: Veerle
authors.initials: V
authors.lastname: De Boe
authors.forename: Agapios
authors.initials: A
authors.lastname: Sachinidis
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.forename: Tamara
authors.initials: T
authors.lastname: Vanhaecke
authors.forename: Laurence
authors.initials: L
authors.lastname: Lagneaux
authors.forename: Vera
authors.initials: V
authors.lastname: Rogiers
authors.forename: Mehdi
authors.initials: M
authors.lastname: Najar
mesh_terms: D064591:Allografts / Q000276:immunology*; D000818:Animals; D018920:Coculture Techniques; D015232:Dinoprostone / Q000096:biosynthesis; D005434:Flow Cytometry; D006680:HLA Antigens / Q000096:biosynthesis; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D053605:Leukemia Inhibitory Factor / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000276:immunology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology* / Q000276:immunology*
chemical_list: C066855:HGF protein, human; D006680:HLA Antigens; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D017228:Hepatocyte Growth Factor; D015232:Dinoprostone
keywords: Adult stem cells; Cell adhesion molecules; Immunogenicity; Immunosuppression; Immunotherapy; Interleukin; Progenitor cells; Stem cell-microenvironment interactions