title: Inhibition effect of blunting Notch signaling on food allergy through improving TH1/TH2 balance in mice.
abstract: Notch signaling regulates proliferation, differentiation, and function of dendritic cells, T cells, and mast cells, as well as many other immune cells, which act as important parts in food allergy, Notch signaling may play an important role in food allergy.
  
  
  
  To investigate the role of Notch signaling in IgE-mediated food allergy.
  
  
  
  An ovalbumin-induced food allergy mouse model was built (cholera toxin as adjuvant) and Notch signaling was blunted by FLI-06 and MW167, which inhibited Notch receptor-expressing phase and the γ-secretase-affecting phase, respectively. Then food allergy indicators, including levels of serum antibodies, cytokines, and degranulation, were examined. Meanwhile, clinical features, such as vascular permeability changes, intestinal permeability changes, body temperature changes, and symptoms, were also observed.
  
  
  
  After blunting Notch signaling, the levels of serum ovalbumin specific IgE and IgG1were decreased significantly, suggesting that blunting Notch signaling inhibited antibody responses. The levels of TH1 cytokines (interferon-γ) were increased significantly, whereas the levels of TH2 cytokines (interleukin-4, -5, and -13) were decreased significantly, suggesting TH2 polarization was suppressed after blunting Notch signaling. The expression of T-bet was significantly increased, whereas the expression of Gata-3 was significantly reduced in both messenger RNA and protein levels, indicating TH2 polarization was inhibited and TH1 polarization was enhanced after blunting Notch signaling. Moreover, allergic clinical features of mice were alleviated after blunting Notch signaling.
  
  
  
  Food allergy was inhibited by blunting Notch signaling through suppressing TH2 polarization, enhancing TH1 cell differentiation and promoting TH1/TH2 balance in mice. Notch signaling plays a key role in IgE-mediated food allergy.
authors.affiliation: College of Food Science and Nutrition Engineering, China Agricultural University, Beijing, China.
authors.forename: Songsong
authors.initials: S
authors.lastname: Jiang
authors.affiliation: College of Food Science and Nutrition Engineering, China Agricultural University, Beijing, China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Han
authors.affiliation: College of Food Science and Nutrition Engineering, China Agricultural University, Beijing, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Chen
authors.affiliation: College of Food Science and Nutrition Engineering, China Agricultural University, Beijing, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Food Science and Nutrition Engineering, China Agricultural University, Beijing, China; Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing, China. Electronic address: chehuilian@cau.edu.cn.
authors.forename: Huilian
authors.initials: H
authors.lastname: Che
mesh_terms: D000818:Animals; D015415:Biomarkers; D002199:Capillary Permeability; D015550:Cell Degranulation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology* / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D018655:Lymphocyte Count; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010455:Peptides / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D050990:GATA3 Transcription Factor; D007132:Immunoglobulin Isotypes; C432344:MW167; D010455:Peptides; D011804:Quinolines; D051880:Receptors, Notch; C000621625:cyclohexyl 2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate