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.
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: Jun-Ichiro Koga; Toshiaki Nakano; James E Dahlman; Jose-Luiz Figueiredo; Hengmin Zhang; Julius Decano; Omar F Khan; Tomiharu Niida; Hiroshi Iwata; Jon C Aster; Hideo Yagita; Daniel G Anderson; C Keith Ozaki; Masanori Aikawa Journal: Arterioscler Thromb Vasc Biol Date: 2015-09-24 Impact factor: 8.311
Authors: Daiju Fukuda; Elena Aikawa; Filip K Swirski; Tatiana I Novobrantseva; Victor Kotelianski; Cem Z Gorgun; Aleksey Chudnovskiy; Hiroyuki Yamazaki; Kevin Croce; Ralph Weissleder; Jon C Aster; Gökhan S Hotamisligil; Hideo Yagita; Masanori Aikawa Journal: Proc Natl Acad Sci U S A Date: 2012-06-13 Impact factor: 11.205