title: Highly expressed cytoplasmic FcεRIβ in human mast cells functions as a negative regulator of the FcRγ-mediated cell activation signal.
abstract: BACKGROUND
  We recently reported that the interaction between Lyn and FcεRIβ is indispensable for FcεRI-mediated human mast cell (MC) activation and that FcεRIβ functions as an amplifier of FcεRI-mediated activation signal. Some of FcεRIβ in cytoplasm appeared not to be co-localized with FcεRIα. The function of FcεRIβ in the cytoplasm remains unknown.
  
  
  METHODS
  The localization of FcεRIβ and FcεRIα in giant papillae specimens from patients with allergic keratoconjunctivitis and of FcεRIβ, FcεRIα, and Lyn in cultured human MCs was examined using confocal microscopy. FcεRIβ was overexpressed using an adenovirus vector system. Mediators were measured by enzyme immunoassays or enzyme-linked immunosorbent assays.
  
  
  RESULTS
  In the subepithelial region, FcεRIβ was mainly localized in the cell membrane of MCs. In the perivascular region, FcεRIβ expression was scattered throughout the cytoplasm and in the cell membrane of MCs. Overexpression of FcεRIβ in MCs mainly increased its cytoplasmic expression and slightly up-regulated cell surface FcεRI expression. However, overexpression of FcεRIβ in MCs resulted in down-regulation of the tyrosine phosphorylation levels of FcεRIβ and Syk and down-regulation of the Ca(2+) influx soon after FcεRI aggregation and then resulted in down-regulation of degranulation, PGD2 synthesis, and production of a set of cytokines. This negative regulatory effect may be due to inhibition of the redistribution of Lyn to small patches within the plasma membrane.
  
  
  CONCLUSIONS
  Cytoplasmic FcεRIβ, which is not co-localized with FcεRIα, may function as a negative regulator, as it can capture important signalling molecules such as Lyn.
authors.affiliation: Allergy and Immunology Group, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okayama
authors.forename: A
authors.initials: A
authors.lastname: Matsuda
authors.forename: J-I
authors.initials: JI
authors.lastname: Kashiwakura
authors.forename: T
authors.initials: T
authors.lastname: Sasaki-Sakamoto
authors.forename: S
authors.initials: S
authors.lastname: Nunomura
authors.forename: T
authors.initials: T
authors.lastname: Shimokawa
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: C
authors.initials: C
authors.lastname: Ra
mesh_terms: D000328:Adult; D020013:Calcium Signaling; D002460:Cell Line; D003593:Cytoplasm; D015536:Down-Regulation; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D007637:Keratoconjunctivitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000276:immunology; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000276:immunology / Q000378:metabolism
chemical_list: C475664:FCER1A protein, human; D047908:Intracellular Signaling Peptides and Proteins; C502447:MS4A2 protein, human; D017455:Receptors, IgE; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases
keywords: Lyn; allergic keratoconjunctivitis; cytoplasmic FcεRIβ; histamine; human mast cells; perivascular region