title: Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 regulates the migration of Langerhans cells from the epidermis to draining lymph nodes.
abstract: Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1) is a member of the signal regulatory protein family in which the extracellular region interacts with its ligand, CD47. Recent studies have demonstrated that SHPS-1 plays an important role in cell migration and cell adhesion. We demonstrate in this study, using immunohistochemical and flow cytometric analyses, that murine Langerhans cells (LCs) express SHPS-1. Treatment of mice ears with 2,4-dinitro-1-fluorobenzene significantly reduced the number of epidermal LCs, and that reduction could be reversed by pretreatment with mAb to SHPS-1 or the CD47-Fc fusion protein. Treatment with the SHPS-1 mAb in vivo reduced the number of FITC-bearing cells in the lesional lymph nodes after the application of FITC to the skin. The SHPS-1 mAb inhibited the in vivo TNF-alpha-induced migration of LCs. The emigration of dendritic cells expressing I-A(b+) from skin explants to the medium was also reduced by the SHPS-1 mAb. We further demonstrate that the chemotaxis of a murine dendritic cell line, XS52, by macrophage inflammatory protein-3beta was significantly inhibited by treatment with the SHPS-1 mAb or CD47-Fc recombinant protein. Finally, we show that migration of LCs was attenuated in mutant mice that lack the intracellular domain of SHPS-1. These observations show that the ligation of SHPS-1 with the SHPS-1 mAb or with CD47-Fc abrogates the migration of LCs in vivo and in vitro, which suggests that the SHPS-1-CD47 interaction may negatively regulate LC migration.
authors.affiliation: Division of Dermatology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukunaga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagai
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Noguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Okazawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Matozaki
authors.forename: Xijun
authors.initials: X
authors.lastname: Yu
authors.forename: Carl F
authors.initials: CF
authors.lastname: Lagenaur
authors.forename: Nakayuki
authors.initials: N
authors.lastname: Honma
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Ichihashi
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Horikawa
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015703:Antigens, CD / Q000008:administration & dosage / Q000235:genetics; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D039521:CD11c Antigen / Q000096:biosynthesis; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000008:administration & dosage / Q000235:genetics; D002452:Cell Count; D002460:Cell Line; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology*; D003470:Culture Media; D004139:Dinitrofluorobenzene / Q000008:administration & dosage; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage; D006241:Haptens / Q000008:administration & dosage / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007271:Injections, Intradermal; D015847:Interleukin-4 / Q000494:pharmacology; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039842:Neural Cell Adhesion Molecule L1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D009924:Organ Culture Techniques; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D039521:CD11c Antigen; D051928:CD47 Antigen; D002352:Carrier Proteins; C497895:Cd47 protein, mouse; D003470:Culture Media; D006131:Growth Inhibitors; D006241:Haptens; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; D007141:Immunoglobulin Fc Fragments; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D004139:Dinitrofluorobenzene