title: Differential effects of cytokines and immunosuppressive drugs on CD40, B7-1, and B7-2 expression on purified epidermal Langerhans cells1.
abstract: Langerhans cells are MHC class II antigen-positive antigen-presenting cells in the epidermis. Recent studies have revealed that Langerhans cells express costimulatory molecules like B7-1 and B7-2 and the accessory molecule CD40. Although these molecules are important for the antigen-presenting function of Langerhans cells, little is known about the precise regulation of their expression on purified Langerhans cells. Using a panning technique, we purified epidermal Langerhans cells to around 95% purity. Freshly prepared Langerhans cells (fLC) expressed the mRNA for receptors for M-CSF (cfms), GM-CSF (GM-CSFR), and TNF-alpha (TNFRII). TNF-alpha markedly upregulated CD40 and B7-1 expression on Langerhans cells, but not B7-2 expression. GM-CSF moderately upregulated B7-1 and B7-2 expression, and slightly upregulated CD40 expression. M-CSF moderately upregulated B7-1 expression, but did not modulate CD40 or B7-2 expression. Dexamethasone (DEX) markedly inhibited CD40, B7-1, and B7-2 expression on Langerhans cells. Cyclosporin A (CsA) and FK506 slightly inhibited CD40 and B7-1 expression on Langerhans cells, but not B7-2. Furthermore, TNF-alpha restored the DEX-induced inhibition of CD40 expression on Langerhans cells, but not the inhibition of B7-1 or B7-2 expression. GM-CSF restored DEX-induced inhibition of CD40, B7-1, and B7-2 expression. M-CSF did not affect the DEX-induced inhibition of these molecule expressions. These data provide a better understanding of the role of selective cytokines and immunosupressive drugs in the modulation of the antigen-presenting capacity of Langerhans cells.
authors.affiliation: Department of Dermatology, The University of Tokyo, Japan.
authors.forename: C G
authors.initials: CG
authors.lastname: Salgado
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Sugaya
authors.forename: Y
authors.initials: Y
authors.lastname: Tada
authors.forename: A
authors.initials: A
authors.lastname: Asahina
authors.forename: S
authors.initials: S
authors.lastname: Fukuda
authors.forename: Y
authors.initials: Y
authors.lastname: Koyama
authors.forename: S
authors.initials: S
authors.lastname: Irie
authors.forename: K
authors.initials: K
authors.lastname: Tamaki
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D018122:B7-1 Antigen / Q000032:analysis*; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000032:analysis*; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007801:Langerhans Cells / Q000737:chemistry / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000032:analysis*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000166:cytology
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D016207:Cytokines; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D003907:Dexamethasone