title: Rosiglitazone promotes the differentiation of Langerhans cells and inhibits that of other dendritic cell types from CD133 positive hematopoietic precursors.
abstract: Dendritic cells and their precursors express PPAR-gamma, whose stimulation has inhibitory effects on the maturation and function of dendritic cells in vivo. Dendritic cells can differentiate in vitro from CD133+ progenitors; the influence of PPAR-gamma stimulation on this process is unknown. We have addressed the effect of PPAR-gamma agonist rosiglitazone, at a concentration as used in clinics, on the differentiation of dendritic cells from human CD133+ progenitors. Cells were harvested from cord blood by density gradient and immunomagnetic separation, and cultured for 18 days with fetal calf serum, cytokines and 1 μmol/L rosiglitazone. Analyses included flow cytometry, electron microscopy and mixed lymphocyte reaction. As expected, control cells generated without rosiglitazone were dendritic, expressed MHC-II, CD80, CD83 and CD86 and stimulated mixed reaction potently. A minority of cells expressed the Langerhans cell marker CD207/langerin, but none contained Birbeck granules. With rosiglitazone much fewer cells were generated; they were all dendritic, expressed differentiation and maturation-related antigens in higher percentage and were better stimulators of lymphocytes than those generated without the drug. The vast majority of cells expressed CD207/langerin and many contained Birbeck granules, i.e. were full-fledged Langerhans cells. We conclude that stimulation of PPAR-gamma, while negatively affecting the number of generated cells, promotes the maturation of human cord blood CD133 positive precursors into efficient, immunostimulating dendritic cells with a Langerhans cell phenotype.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Maria Ida
authors.initials: MI
authors.lastname: Bonetti
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. stefano.bacci@unifi.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bacci
authors.affiliation: Haematology Unit, University Hospital Careggi, Florence, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Santosuosso
authors.affiliation: Haematology Unit, University Hospital Careggi, Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzanti
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health (NeuroFarBa), University of Florence, Florence, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Aldinucci
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health (NeuroFarBa), University of Florence, Florence, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Ballerini
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Guasti
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Calosi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, and Haematology Unit, University Hospital Careggi, Florence, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Romagnoli
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005312:Fetal Blood; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018189:Immunomagnetic Separation; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007959:Lymphocyte Culture Test, Mixed; D046529:Microscopy, Electron, Transmission; D047495:PPAR gamma / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D047495:PPAR gamma; C000606023:PROM1 protein, human; D010455:Peptides