ヒト疾患モデル研究センターセミナー・生命研合同セミナー
日時 2017 年 11 月 9 日(木) 16:30~18:00
場所 東京理科大学生命医科学研究所2階大講義室
場所 東京理科大学生命医科学研究所2階大講義室
Speaker Hidehiro Yamane, PhD
Cellular Immunology Section,
Cellular Immunology Section,
Laboratory of Immune System Biology,
National Institute of Allergy and Infectious Diseases,
National Institutes of Health, USA
National Institute of Allergy and Infectious Diseases,
National Institutes of Health, USA
Title
Mechanisms underlying the fine-tuning of CD4+ T cell positioning during T follicular helper cell differentiation
Abstract
T follicular helper (TFH) cells are a subset of T helper cells that helps B cells produce immunoglobulin (Ig) and induce class switch recombination and somatic hypermutation in the Ig genes upon encounter with a T-dependent antigen (Ag). Differentiation of naïve CD4+ T cells into functional TFH cells involves not only a transcriptional regulation of signature TFH-related genes, a set of genes that drives TFH polarization program, but an alteration in the expression of chemoattractant receptors, integrins and their ligands, since a subcellular localization of Ag-primed CD4+ T cells in the secondary lymphoid organs is spaciotemporally regulated during TFH differentiation. We recently found that an E-box binding protein family of transcription factors HEB and Notch signaling pathway played crucial roles in the entry of Ag-primed CD4+ T cells that had undergone the TFH polarization program into B cell follicles and germinal centers, respectively, with little or no impact on the signature TFH-related gene expressions. Our findings shed a light to unappreciated functions of HEB and Notch pathway in fine-tuning the positioning of Ag-primed CD4+ T cells during the differentiation into functional TFH cells and may offer novel strategies for the development of effective antibody-based vaccines.
T follicular helper (TFH) cells are a subset of T helper cells that helps B cells produce immunoglobulin (Ig) and induce class switch recombination and somatic hypermutation in the Ig genes upon encounter with a T-dependent antigen (Ag). Differentiation of naïve CD4+ T cells into functional TFH cells involves not only a transcriptional regulation of signature TFH-related genes, a set of genes that drives TFH polarization program, but an alteration in the expression of chemoattractant receptors, integrins and their ligands, since a subcellular localization of Ag-primed CD4+ T cells in the secondary lymphoid organs is spaciotemporally regulated during TFH differentiation. We recently found that an E-box binding protein family of transcription factors HEB and Notch signaling pathway played crucial roles in the entry of Ag-primed CD4+ T cells that had undergone the TFH polarization program into B cell follicles and germinal centers, respectively, with little or no impact on the signature TFH-related gene expressions. Our findings shed a light to unappreciated functions of HEB and Notch pathway in fine-tuning the positioning of Ag-primed CD4+ T cells during the differentiation into functional TFH cells and may offer novel strategies for the development of effective antibody-based vaccines.
世話人:
岩倉洋一郎
東京理科大学
生命医科学研究所
ヒト疾患モデル研究センター