title: Transcription factor E3, a major regulator of mast cell-mediated allergic response.
abstract: BACKGROUND
  Microphthalmia transcription factor, an MiT transcription family member closely related to transcription factor E3 (TFE3), is essential for mast cell development and survival. TFE3 was previously reported to play a role in the functions of B and T cells; however, its role in mast cells has not yet been explored.
  
  
  OBJECTIVE
  We sought to explore the role played by TFE3 in mast cell function.
  
  
  METHODS
  Mast cell numbers were evaluated by using toluidine blue staining. FACS analysis was used to determine percentages of Kit and FcεRI double-positive cells in the peritoneum of wild-type (WT) and TFE3 knockout (TFE3(-/-)) mice. Cytokine and inflammatory mediator secretion were measured in immunologically activated cultured mast cells derived from either knockout or WT mice. In vivo plasma histamine levels were measured after immunologic triggering of these mice.
  
  
  RESULTS
  No significant differences in mast cell numbers between WT and TFE3(-/-) mice were observed in the peritoneum, lung, and skin. However, TFE3(-/-) mice showed a marked decrease in the number of Kit(+) and FcεRI(+) peritoneal and cultured mast cells. Surface expression levels of FcεRI in TFE3(-/-) peritoneal mast cells was significantly lower than in control cells. Cultured mast cells derived from TFE3(-/-) mice showed a marked decrease in degranulation and mediator secretion. In vivo experiments showed that the level of plasma histamine in TFE3(-/-) mice after an allergic trigger was substantially less than that seen in WT mice.
  
  
  CONCLUSIONS
  TFE3 is a novel regulator of mast cell functions and as such could emerge as a new target for the manipulation of allergic diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yagil
authors.forename: Tal
authors.initials: T
authors.lastname: Hadad Erlich
authors.forename: Yifat
authors.initials: Y
authors.lastname: Ofir-Birin
authors.forename: Sagi
authors.initials: S
authors.lastname: Tshori
authors.forename: Gillian
authors.initials: G
authors.lastname: Kay
authors.forename: Zanna
authors.initials: Z
authors.lastname: Yekhtin
authors.forename: David E
authors.initials: DE
authors.lastname: Fisher
authors.forename: Chang
authors.initials: C
authors.lastname: Cheng
authors.forename: W S Fred
authors.initials: WS
authors.lastname: Wong
authors.forename: Karin
authors.initials: K
authors.lastname: Hartmann
authors.forename: Ehud
authors.initials: E
authors.lastname: Razin
authors.forename: Hovav
authors.initials: H
authors.lastname: Nechushtan
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015550:Cell Degranulation / Q000235:genetics; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D006632:Histamine / Q000235:genetics / Q000378:metabolism; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007114:Immunization; D018836:Inflammation Mediators / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics; D010537:Peritoneum / Q000473:pathology; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D016207:Cytokines; D018836:Inflammation Mediators; D051739:Microphthalmia-Associated Transcription Factor; D017455:Receptors, IgE; C068486:Tcfe3 protein, mouse; D006632:Histamine