title: Notch ligand Delta-like4 inhibits the development of murine experimental allergic conjunctivitis.
abstract: BACKGROUND
  To investigate the involvement of Notch ligands in the development of experimental allergic conjunctivitis (EC) in mice.
  
  
  METHODS
  To induce EC, wild-type (WT) or IFN-gamma-deficient (GKO) BALB/c mice were immunized with ragweed (RW) in alum followed by RW challenge in eye drops. Twenty-four hours after RW challenge, the conjunctivas, spleens and blood were harvested to evaluate conjunctival eosinophil infiltration, RW-specific cytokine production and serum Ig levels, respectively. Abs against Notch ligands (anti-Jagged1, anti-Jagged2, anti-Delta-like (Dll)1 and anti-Dll4) were injected intraperitoneally into EC-developing mice during the induction or effector phase. As a control, normal hamster IgG (nhIgG) was injected.
  
  
  RESULTS
  Treatment with anti-Dll4 Ab but not the other Abs during the induction phase significantly augmented the severity of EC, as measured by the conjunctival eosinophil infiltration. Anti-Dll4 Ab treatment also significantly upregulated RW-recall IL-4 production and suppressed serum IgE and IgG1 levels. However, anti-Dll4 Ab treatment during the induction phase did not significantly affect the severity of EC in GKO mice. None of the Abs significantly affected the severity of EC, splenocyte cytokine production, or serum Ig levels when administered during the effector phase.
  
  
  CONCLUSIONS
  These observations suggest that Dll4, a Notch ligand, plays a role in suppressing the development of EC, possibly by providing a negative signal for Th2 development during the induction phase. In addition, IFN-gamma may participate in the augmentation of EC by anti-Dll4 Ab treatment.
authors.affiliation: Department of Ophthalmology and Visual Science, Kochi Medical School, Nankoku, Japan. fukusima@kochi-u.ac.jp
authors.forename: Atsuki
authors.initials: A
authors.lastname: Fukushima
authors.forename: Tamaki
authors.initials: T
authors.lastname: Sumi
authors.forename: Waka
authors.initials: W
authors.lastname: Ishida
authors.forename: Ayako
authors.initials: A
authors.lastname: Ojima
authors.forename: Mina
authors.initials: M
authors.lastname: Kajisako
authors.forename: Akemi
authors.initials: A
authors.lastname: Koyanagi
authors.forename: Noriko
authors.initials: N
authors.lastname: Koyama
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000534:Alum Compounds; D031164:Ambrosia; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D002135:Calcium-Binding Proteins; D003228:Conjunctiva / Q000276:immunology / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007117:Immunization, Secondary; D007136:Immunoglobulins / Q000097:blood; D007371:Interferon-gamma / Q000172:deficiency; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000534:Alum Compounds; D019138:Antibodies, Blocking; D002135:Calcium-Binding Proteins; D016207:Cytokines; C519665:DLL4 protein, mouse; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C041524:aluminum sulfate; D007371:Interferon-gamma