Molecular characterization of survival niches for memory T helper cells in bone marrow

骨髓中记忆 T 辅助细胞生存位的分子特征

• 批准号: 310702922
• 负责人: Dr. Koji Tokoyoda
• 金额: --
• 依托单位: Deutsches Rheuma-Forschungszentrum Berlin (DRFZ)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/310702922?language=en
• 关键词: Molecular; characterization; survival; niches; memory

Recently, I have described that in distinct murine immune responses memory T helper (Th) cells preferentially if not exclusively reside and rest in the bone marrow (BM). CD4 T cells after activation in secondary lymphoid organs (SLOs) immigrate into the BM in a CD69- and CD49b (a collagen receptor)-dependent manner and localize as memory Th cells, expressing Ly-6C and CD44, to survival niches organized by collagen XI+IL-7+ stromal cells of the BM. The molecules mediating the survival and residency of memory Th cells in the BM are not known. The project proposed aims at the identification of cytokines, chemokines and adhesion molecules involved in the maintenance of memory Th cells in the BM. In particular, I will (i) determine the roles of the CD49b and its ligand collagen XI, and of IL-7 and its receptor, and (ii) identify other factors involved in the maintenance of memory Th cells. This project will achieve a molecular understanding of how the memory Th cells are kept in quiescence and survive in their BM niches, in the apparent absence of antigen.

最近，我描述了在不同的小鼠免疫反应中，记忆T辅助(Th)细胞优先(如果不是唯一的话)驻留在骨髓(BM)中。CD4T细胞在次级淋巴器官(SLO)激活后，以CD69和CD49b(一种胶原受体)依赖的方式迁移到BM中，并定位为记忆性Th细胞，表达Ly-6C和CD44，定位于由BM中的胶原XI+IL-7+基质细胞组成的生存生态位。调节记忆Th细胞在骨髓中存活和驻留的分子尚不清楚。该项目旨在鉴定参与维持骨髓中记忆Th细胞的细胞因子、趋化因子和黏附分子。特别是，我将(I)确定CD49b及其配基胶原蛋白XI和IL-7及其受体的作用，以及(Ii)确定与维持记忆Th细胞有关的其他因素。这个项目将实现对记忆Th细胞如何在明显缺乏抗原的情况下保持静止并在其BM利基中存活的分子理解。

项目成果

Enhanced Cell Division Is Required for the Generation of Memory CD4 T Cells to Migrate Into Their Proper Location

记忆 CD4 T 细胞的生成需要增强的细胞分裂才能迁移到正确的位置

• DOI: 10.3389/fimmu.2019.03113
• 发表时间: 2020
• 期刊: Frontiers in Immunology
• 影响因子: 7.3
• 作者: Sarkander J;Hojyo S;Mursell M;Yamasaki Y;Tumes DT;Miyauchi K;Tran CT;Löhning M;Hutloff A;Mashreghi MF;Kubo M;Radbruch A;Tokoyoda K
• 通讯作者: Tokoyoda K

Ezh2 controls development of natural killer T cells, which cause spontaneous asthma-like pathology.

• DOI: 10.1016/j.jaci.2019.02.024
• 发表时间: 2019-08
• 期刊: The Journal of allergy and clinical immunology
• 作者: D. Tumes;K. Hirahara;Magdalene Papadopoulos;K. Shinoda;A. Onodera;J. Kumagai;K. Yip;Harshita Pant;Kota Kokubo;M. Kiuchi;A. Aoki;K. Obata-Ninomiya;K. Tokoyoda;Yusuke Endo;M. Kimura;T. Nakayama

Multiplexed fluorescence microscopy reveals heterogeneity among stromal cells in mouse bone marrow sections

• DOI: 10.1002/cyto.a.23526
• 发表时间: 2018-09-01
• 期刊: CYTOMETRY PART A
• 影响因子: 3.7
• 作者: Holzwarth, Karolin;Koehler, Ralf;Hauser, Anja E.
• 通讯作者: Hauser, Anja E.

Salmonella SiiE prevents an efficient humoral immune memory by interfering with IgG+ plasma cell persistence in the bone marrow

• DOI: 10.1073/pnas.1818242116
• 发表时间: 2019-04-09
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Maenne, Christian;Takaya, Akiko;Tokoyoda, Koji
• 通讯作者: Tokoyoda, Koji