title: Flagellin modulates TIM4 expression in mast cells.
abstract: T-helper (Th) 2 polarization functions in a number of immune diseases, but their pathogenesis needs further investigation. Some microbial products or components are strong adjuvants in the creation of mouse models of Th2 polarization. T cell immunoglobulin mucin molecule (TIM) 4 is a facilitator in the initiation of Th2 response. This study looks at the role of one of the microbial products, flagellin (FGN), in the induction of TIM4 expression in mast cells. Bone marrow derived mast cells (BMMC) were generated. Induction of TIM4 in mast cells was assessed in both experiments in vitro and in vivo. The signal transducer and activator of transcription 6 (Stat6) phosphorylation in BMMC were assessed by Western blotting. A coculture model with FGN-primed BMMC and naïve CD4(+) T cells was employed to assess FGN in facilitating the expression of TIM4 in mast cells. After exposure to FGN, TIM4 levels were significantly increased in BMMC and mast cells of the mouse intestine, which was accompanied by increased STAT6 phosphorylation. Culture with FGN-primed BMMC, naïve CD4(+) T cells developed into Th2 cells by a TIM4-dependent manner. We conclude that FGN can induce mast cells to express TIM4, which helps initiate Th2 polarization.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Linjing
authors.initials: L
authors.lastname: Li
authors.forename: Lihua
authors.initials: L
authors.lastname: Mo
authors.forename: Huijie
authors.initials: H
authors.lastname: Hao
authors.forename: Wanhe
authors.initials: W
authors.lastname: Yang
authors.forename: Quanbo
authors.initials: Q
authors.lastname: Zhou
authors.forename: Fumin
authors.initials: F
authors.lastname: Xue
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Shi
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
authors.forename: Baisui
authors.initials: B
authors.lastname: Feng
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005408:Flagellin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D050800:STAT6 Transcription Factor / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology
chemical_list: D008565:Membrane Proteins; D050800:STAT6 Transcription Factor; C500399:TIM-4 protein, mouse; D005408:Flagellin
keywords: T helper 2; TIM4; adjuvant; flagellin; mast cells