title: Flagellin modulates IgE expression in B cells to initiate food allergy in mice.
abstract: The initiation mechanism of IgE expression has not been fully understood. Flagellin (FGN) is an important microbial factor in the regulation of immune responses in the intestine. This study tests a hypothesis that FGN plays a crucial role in the isotype switching of IgE in B cells and the initiation of food allergy. In this study, the expression of IgE in B cells was analyzed by real time RT-PCR, Western blotting and chromatin immunoprecipitation. A mouse model was developed to assess the role of Toll like receptor-5 in the development of IgE-mediated allergic reaction in the intestinal mucosa. The results showed that exposure to FGN suppressed the expression of Bcl6 in B cells via increasing the levels of histone deacetylase (HDAC) 7; the latter up regulated the levels of methylated H3K9 and H3K27, down regulated RNA polymerase II and STAT3 (signal transducer and activator of transcription 3) at the Bcl6 promoter locus. Exposure to FGN and IL-4 markedly increased the expression of IgE in B cells via activating p300, H3K4, Pol II and STAT6 at the IgE promoter locus. As compared with the sensitized wild mice, the sensitized TLR5-deficient mice showed no detectable OVA-specific IgE in the serum; mast cells in the intestinal mucosa were not activated, no apparent allergic symptoms were evoked after the specific antigen challenge. In conclusion, FGN facilitates the initiation of food allergy in mice by triggering IgE transcription in B cells in a Th2 polarization environment via activating HDAC7 and suppressing Bcl6 expression.
authors.affiliation: Department of Gastroenterology, The First Hospital, Zhengzhou UniversityZhengzhou 450052, China; Brain Body Institute and Department of Pathology & Molecular Medicine, McMaster UniversityHamilton, ON, L8N 3Z5, Canada.
authors.forename: Lin-Jing
authors.initials: LJ
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The First Hospital, Zhengzhou UniversityZhengzhou 450052, China; The Research Center of Allergy & Immunology, Shenzhen University School of MedicineShenzhen 518060, China.
authors.forename: Na
authors.initials: N
authors.lastname: Ma
authors.affiliation: The Research Center of Allergy & Immunology, Shenzhen University School of Medicine Shenzhen 518060, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zeng
authors.affiliation: The Research Center of Allergy & Immunology, Shenzhen University School of Medicine Shenzhen 518060, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Mo
authors.affiliation: The Research Center of Allergy & Immunology, Shenzhen University School of Medicine Shenzhen 518060, China.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Li
authors.affiliation: The Research Center of Allergy & Immunology, Shenzhen University School of Medicine Shenzhen 518060, China.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Xu
authors.affiliation: The Research Center of Allergy & Immunology, Shenzhen University School of Medicine Shenzhen 518060, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: The Research Center of Allergy & Immunology, Shenzhen University School of Medicine Shenzhen 518060, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Second Hospital, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Bai-Sui
authors.initials: BS
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, The Fifth Hospital, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Zheng
authors.affiliation: Brain Body Institute and Department of Pathology & Molecular Medicine, McMaster University Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Huan-Ping
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: The Research Center of Allergy & Immunology, Shenzhen University School of Medicine Shenzhen 518060, China.
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
keywords: Allergy; B cell lymphoma-6; B lymphocyte; Toll like receptor-5; flagellin