Rosiglitazone promotes the differentiation of Langerhans cells and inhibits that of other dendritic cell types from CD133 positive hematopoietic precursors

• Autores: Maria Ida Bonetti, Stefano Bacci, Michela Santosuosso, Benedetta Mazzanti, Alessandra Aldinucci, Clara Ballerini, Daniele Guasti, Laura Calosi, Alberto Bosi, Paolo Romagnoli
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 29, Nº. 3, 2014, págs. 323-332
• Idioma: inglés
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  • 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.