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Adhesive interactions governing immune-cell trafficking across HEVs and its regulation by infectious stimulation

Adhesive interactions governing immune-cell trafficking across HEVs and its regulation by infectious stimulation
控制跨 HEV 免疫细胞运输的粘附相互作用及其通过感染刺激的调节
批准号:
17590432
负责人:
TANAKA Toshiyuki
金额:
$2.3万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2005
资助国家:
日本
项目状态:
已结题
起止时间:
2005 至 2006

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中文摘要
翻译
淋巴细胞和某些抗原呈递细胞从血液转运到淋巴结(LN)是由循环免疫细胞和高内皮小静脉(HEVs)之间的级联粘附相互作用介导的。粘附相互作用包括免疫细胞在hev上的滚动、牢固粘附和跨内皮迁移。控制粘附相互作用的分子机制仍有待充分阐明。在这里,我们解决了以下两个问题。(1)一种新型唾液黏液蛋白nepmucin在淋巴细胞归巢中的功能意义。我们发现了一种新的hev相关的唾液黏液蛋白,nepmucin(在Peyer’s patches中不表达的黏液蛋白)。与传统的黏液蛋白不同,nepmucin含有一个单一的v型Ig结构域和一个黏液蛋白样结构域。在LN hev中,内粘蛋白由l -选择蛋白反应性糖链修饰。我们发现用l -选择蛋白活性低聚糖修饰的粘蛋白样结构域支持淋巴细胞在生理流动条件下的滚动。此外,nepmucin通过其Ig结构域结合淋巴细胞,明显独立于淋巴细胞LFA-1和vla4,并与ICAM-1结合促进抗剪切淋巴细胞的结合。综上所述,这些结果表明,在LN hev中,nepmucin可能作为一种双重功能的粘附分子,通过不同的功能域介导淋巴细胞滚动和结合。(2)浆细胞样树突状细胞(pDCs)与hev的粘附相互作用。pDCs是天然的I型干扰素产生细胞,存在于LNs中,它们支持先天和适应性免疫反应。我们发现pDCs上的LFA-1/VLA-4及其配体在hev上的粘附和迁移过程中起关键作用。我们还发现,通过CCR7传递的信号在HEV细胞内pDCs向LNs的稳态运输中发挥重要作用。这些观察结果共同表明,某些细胞粘附分子和趋化因子信号协同调节混合动力汽车中pDCs的运输。少
英文摘要
Trafficking of lymphocytes and certain antigen presenting cells from the blood into lymph nodes (LN) is mediated by a cascade of adhesive interactions between circulating immune-cells and high endothelial venules (HEVs). The adhesive interactions include rolling, firm adhesion and transendothelial migration of immune-cells across the HEVs. Molecular mechanisms governing the adhesive interactions still remain to be fully elucidated. Here we addressed two following issues. (1)Functional significance of a novel sialomucin nepmucin in lymphocyte homing to LNs. We identified a novel HEV-associated sialomucin, nepmucin (mucin not expressed in Peyer's patches). Unlike conventional sialomucins, nepmucin contains a single V-type Ig domain and a mucin-like domain. In LN HEVs, nepmucin is decorated by L-selectin-reactive sugar chains. We found that nepmucin modified with L-selectin-reactive oligosaccharides in its mucin-like domain supported lymphocyte rolling under physiological flow conditions. … More Furthermore, nepmucin bound lymphocytes via its Ig domain, apparently independent of lymphocyte LFA-1 and VLA-4,and promoted shear-resistant lymphocyte binding in combination with ICAM-1. Taken together, these results suggest that nepmucin may serve as a dual-functioning adhesion molecule in LN HEVs, mediating both lymphocyte rolling and binding via different functional domains. (2)Adhesive interactions between plasmacytoid dendritic cells (pDCs) and HEVs. pDCs are natural type I interferon-producing cells, and are found in LNs, where they support both innate and adaptive immune responses. We found that LFA-1/VLA-4 on pDCs and their ligands on HEVs play critical roles in the adhesion and transmigration process of pDCs. We also found that signals through CCR7 play an important role in homeostatic trafficking of pDCs into LNs across HEV cells. These observations collectively suggest that certain cell adhesion molecules and chemokine signals cooperatively regulate trafficking of pDCs across HEVs. Less
期刊论文(17)
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会议论文
Review : Chemokines in tumor progression and metastasis.
综述:肿瘤进展和转移中的趋化因子。
DOI: --
发表时间: 2005
期刊: Cancer Sci. 96
影响因子: --
作者: [Tanaka, T. et al.]
通讯作者: T. et al.
Invasive human pancreatic carcinoma cells adhere to endothelial tri-cellular corners and increase endothelial permeability.
侵袭性人胰腺癌细胞粘附于内皮三细胞角并增加内皮通透性。
DOI: --
发表时间: 2005
期刊: Cancer Sci. 96
影响因子: --
作者: [Nakai, K., Tanaka, T., Murai, T., Ohguro, N., Tano, Y., Miyasaka, M.]
通讯作者: M.
DOI: 10.4049/jimmunol.178.4.2499
发表时间: 2007-02-15
期刊: JOURNAL OF IMMUNOLOGY
影响因子: 4.4
作者: [Matsumoto, Masanori, Shigeta, Akiko, Hirata, Takako]
通讯作者: Hirata, Takako
DOI: 10.1084/jem.20052543
发表时间: 2006-06-12
期刊: The Journal of experimental medicine
影响因子: --
作者: [Umemoto E, Tanaka T, Kanda H, Jin S, Tohya K, Otani K, Matsutani T, Matsumoto M, Ebisuno Y, Jang MH, Fukuda M, Hirata T, Miyasaka M]
通讯作者: Miyasaka M
共 10 条
    Regulation of immune-checkpoint by IL-18 and its application to cancer immunotherapy
    • 批准号:
      18K07305
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $2.83万
    • 财政年份:
      2018
    • 负责人:
      TANAKA Toshiyuki
    • 依托单位:
    Search for enzymes that introduce a triple bond between two carbon atoms and elucidation of their reaction mechanisms
    • 批准号:
      16K14898
    • 项目类别:
      Grant-in-Aid for Challenging Exploratory Research
    • 资助金额:
      $2.33万
    • 财政年份:
      2016
    • 负责人:
      TANAKA Toshiyuki
    • 依托单位:
    Fresh concrete collective diagnosis using electromagnetic waves and Improvement of electromagnetic wave radar method
    • 批准号:
      26420461
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $3.16万
    • 财政年份:
      2014
    • 负责人:
      TANAKA Toshiyuki
    • 依托单位:
    Development of Rapid, Sensitive and Concurrent Multiple Immunoassay of Disease Markers: Construction by Using Fluorescent Magnetic Beads
    • 批准号:
      26860364
    • 项目类别:
      Grant-in-Aid for Young Scientists (B)
    • 资助金额:
      $1.75万
    • 财政年份:
      2014
    • 负责人:
      TANAKA Toshiyuki
    • 依托单位:
    海外基金