title: Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation.
abstract: Recently, we reported that Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1) plays an important role in the migration of Langerhans cells (LC). Here, we show that SHPS-1 is involved in the maturation of LC. Immunofluorescence analysis on epidermal sheets for I-A or CD86 revealed that LC maturation induced by 2,4-dinitro-1-fluorobenzene (DNFB) or by TNF-alpha was inhibited by pretreatment with an anti-SHPS-1 monoclonal antibody (mAb) or with CD47-Fc fusion protein, a ligand for SHPS-1. Further, FACS analysis demonstrated that I-A(+) LC that had emigrated from skin explants expressed CD80 or CD86, whereas CD47-Fc protein reduced CD80(high+) or CD86(high+) cells. CD47-Fc protein also reduced the up-regulation of surface CD80 or CD86 by LC remaining in the skin explants. In SHPS-1 mutant mice, we observed that the up-regulation of surface CD86 and CCR7 by LC induced by DNFB as well as that of surface CD80 and CD86 by LC in skin explants was attenuated. Finally, contact hypersensitivity (CHS) response was suppressed in SHPS-1 mutant mice and in wild-type mice treated with an anti-SHPS-1 mAb. These observations indicate that SHPS-1 plays an important role in the maturation of LC ex vivo and in vivo, and that SHPS-1-CD47 interaction may negatively regulate CHS.
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: Xijun
authors.initials: X
authors.lastname: Yu
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Oniki
authors.forename: Hideki
authors.initials: H
authors.lastname: Okazawa
authors.forename: Sei-ichiro
authors.initials: S
authors.lastname: Motegi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Suzuki
authors.forename: Nakayuki
authors.initials: N
authors.lastname: Honma
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 / Q000627:therapeutic use; D051928:CD47 Antigen / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000276:immunology / Q000517:prevention & control; D005260:Female; D007801:Langerhans Cells / Q000166:cytology* / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009924:Organ Culture Techniques; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D013379:Substrate Specificity / Q000235:genetics / Q000276:immunology; D018909:src Homology Domains / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D051928:CD47 Antigen; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic