title: Engagement of CD47 inhibits the contact hypersensitivity response via the suppression of motility and B7 expression by Langerhans cells.
abstract: CD47 is a membrane-associated glycoprotein that suppresses the function of immune cells. We previously reported that Langerhans cells (LCs) express Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1), a ligand for CD47, which plays an important role in the regulation of their motility. In this study, we show that LCs also express CD47, and that ligation of CD47 with SHPS-1-Fc fusion protein in vivo diminishes the development of the contact hypersensitivity response. We further demonstrate that CD47 engagement affects immune functions of LCs. CD47 engagement in vivo significantly inhibits the emigration of LCs from the epidermis into draining lymph nodes following treatment with haptens and tumor necrosis factor-alpha. The emigration of dendritic cells from skin explants into the medium and the chemotaxis of murine XS52 dendritic cells were significantly reduced by treatment with SHPS-1-Fc or an anti-CD47 mAb. Under explant culture system, SHPS-1-Fc treatment suppressed the expression of CD80 and CD86 of LCs. These effects on LCs and contact hypersensitivity response of CD47 ligation were reversed by treatment with pertussis toxin. These results suggest that the ligation of CD47 inhibits the migration of LCs and the expression of B7 costimulatory molecules, which results in inhibition of the contact hypersensitivity response.
authors.affiliation: Division of Dermatology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Xijun
authors.initials: X
authors.lastname: Yu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukunaga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagai
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Oniki
authors.forename: Nakayuki
authors.initials: N
authors.lastname: Honma
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Ichihashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Matozaki
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Horikawa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism*; D051928:CD47 Antigen / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D015536:Down-Regulation; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D005260:Female; D006241:Haptens / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D037342:Pertussis Toxin / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D051928:CD47 Antigen; D006241:Haptens; D008024:Ligands; D011993:Recombinant Fusion Proteins; C510031:SHPS-1-Fc fusion protein; D015847:Interleukin-4; D037342:Pertussis Toxin