title: Notch signaling in T cells is essential for allergic airway inflammation, but expression of the Notch ligands Jagged 1 and Jagged 2 on dendritic cells is dispensable.
abstract: BACKGROUND
  Allergic asthma is characterized by a TH2 response induced by dendritic cells (DCs) that present inhaled allergen. Although the mechanisms by which they instruct TH2 differentiation are still poorly understood, expression of the Notch ligand Jagged on DCs has been implicated in this process.
  
  
  OBJECTIVE
  We sought to establish whether Notch signaling induced by DCs is critical for house dust mite (HDM)-driven allergic airway inflammation (AAI) in vivo.
  
  
  METHODS
  The induction of Notch ligand expression on DC subsets by HDM was quantified by using quantitative real-time PCR. We used an HDM-driven asthma mouse model to compare the capacity of Jagged 1 and Jagged 2 single- and double-deficient DCs to induce AAI. In addition, we studied AAI in mice with a T cell-specific deletion of recombination signal-binding protein for immunoglobulin Jκ region (RBPJκ), a downstream effector of Notch signaling.
  
  
  RESULTS
  HDM exposure promoted expression of Jagged 1, but not Jagged 2, on DCs. In agreement with published findings, in vitro-differentiated and HDM-pulsed Jagged 1 and Jagged 2 double-deficient DCs lacked the capacity to induce AAI. However, after in vivo intranasal sensitization and challenge with HDM, DC-specific Jagged 1 or Jagged 2 single- or double-deficient mice had eosinophilic airway inflammation and a TH2 cell activation phenotype that was not different from that in control littermates. In contrast, RBPJκ-deficient mice did not experience AAI and airway hyperreactivity.
  
  
  CONCLUSIONS
  Our results show that the Notch signaling pathway in T cells is crucial for the induction of TH2-mediated AAI in an HDM-driven asthma model but that expression of Jagged 1 or Jagged 2 on DCs is not required.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Irma
authors.initials: I
authors.lastname: Tindemans
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Melanie
authors.initials: M
authors.lastname: Lukkes
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Marjolein J W
authors.initials: MJW
authors.lastname: de Bruijn
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Bobby W S
authors.initials: BWS
authors.lastname: Li
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Menno
authors.initials: M
authors.lastname: van Nimwegen
authors.affiliation: Sanquin, Amsterdam, The Netherlands.
authors.forename: Derk
authors.initials: D
authors.lastname: Amsen
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Alex
authors.initials: A
authors.lastname: KleinJan
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands. Electronic address: r.hendriks@erasmusmc.nl.
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D000072100:Jagged-1 Protein / Q000235:genetics / Q000378:metabolism*; D000072101:Jagged-2 Protein / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D039741:Antigens, Dermatophagoides; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D051880:Receptors, Notch
keywords: Allergic asthma; Gata-3; Jagged; Notch signaling; T(H)1 immunity; T(H)2 immunity; cytokines; house dust mite; recombination signal–binding protein for immunoglobulin Jκ region