title: Corticosteroids prevent generation of CD34+-derived dermal dendritic cells but do not inhibit Langerhans cell development.
abstract: Corticosteroids (CS) have been shown to exert strong inhibitory effects on dendritic cell (DC) differentiation and function. Those studies were mostly performed with monocyte-derived DC, which represents only one subpopulation from the wide variety of DC types. In the present study the effects of the CS dexamethasone and prednisolone were investigated on the differentiation of CD34(+) hemopoietic progenitor cells into 1) Langerhans cells (LC), which differentiate directly into CD1a(+) DC; and 2) dermal/interstitial DC, which differentiate via a CD14(+)CD1a(-) phenotype into CD14(-)CD1a(+) DC. CS present during the entire 11-day culture period, resulting in fully differentiated CD1a(+) DC, increased the percentage of langerin(+) DC within the CD1a(+) population. In line with these data, CS treatment during the first 6 days of differentiation reduced the development of CD14(+) dermal DC precursors and thereby seemed to support the generation of CD1a(+) LC precursors. Addition of CS from day 6 onward specifically blocked the development of CD1a(+) dermal DC by both inhibition of spontaneous and IL-4-induced differentiation of CD14(+) DC precursors into CD1a(+) DC as well as induction of apoptosis in CD14(+) DC precursors. Apoptosis was not found in CD14(+) macrophage precursors derived from the same CD34(+) progenitors. The development and function of LC were not affected by CS, as demonstrated by a normal T cell stimulatory capacity and IL-12 production. These data demonstrate that CS interfere with the normal development of DC from CD34(+) progenitors by specific induction of apoptosis in precursors of dermal/interstitial DC. In view of the different functional capacities of dermal/interstitial DC and Langerhans cells, this might affect the overall cellular immune response.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. a.m.woltman@lumc.nl
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Woltman
authors.forename: Catherine
authors.initials: C
authors.lastname: Massacrier
authors.forename: Johan W
authors.initials: JW
authors.lastname: de Fijter
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
mesh_terms: D000328:Adult; D018949:Antigens, CD1 / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; D018952:Antigens, CD34; D006131:Growth Inhibitors; D018950:Lipopolysaccharide Receptors; D003907:Dexamethasone