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: Osaka University
• 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
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590432/
• 关键词: lymphocyte homing; lymph nodes; high endothelial venules; cell adhesion; chemokine; rolling; nepmucin; L-selectin; L-レセレクチン

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

淋巴细胞和某些抗原呈递细胞从血液运输到淋巴结 (LN) 是由循环免疫细胞和高内皮微静脉 (HEV) 之间的一系列粘附相互作用介导的。粘附相互作用包括免疫细胞跨 HEV 的滚动、牢固粘附和跨内皮迁移。控制粘合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)新型唾液粘蛋白​​nepmucin在淋巴细胞归巢至淋巴结中的功能意义。我们鉴定出一种新的与 HEV 相关的唾液粘蛋白​​，nepmucin（派尔氏淋巴结中不表达的粘蛋白）。与传统的唾液粘蛋白​​不同，nepmucin 包含单个 V 型 Ig 结构域和粘蛋白样结构域。在 LN HEV 中，nepmucin 被 L-选择素反应性糖链修饰。我们发现，在其粘蛋白样结构域中用 L-选择素反应性寡糖修饰的 nepmucin 支持淋巴细胞在生理流动条件下滚动。 … 更多此外，nepmucin 通过其 Ig 结构域结合淋巴细胞，显然独立于淋巴细胞 LFA-1 和 VLA-4，并与 ICAM-1 结合促进抗剪切淋巴细胞结合。综上所述，这些结果表明 nepmucin 可能作为 LN HEV 中的双重功能粘附分子，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(pDC)与HEV之间的粘附相互作用。 pDC 是天然的 I 型干扰素产生细胞，存在于 LN 中，支持先天性和适应性免疫反应。我们发现pDC上的LFA-1/VLA-4及其HEV上的配体在pDC的粘附和迁移过程中发挥着关键作用。我们还发现，通过 CCR7 的信号在 pDC 跨 HEV 细胞稳态运输至 LN 中发挥着重要作用。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 pDC 跨 HEV 的运输。较少的

项目成果

Review : Chemokines in tumor progression and metastasis.

综述：肿瘤进展和转移中的趋化因子。

• 发表时间: 2005
• 期刊: Cancer Sci. 96
• 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。

• 发表时间: 2005
• 期刊: Cancer Sci. 96
• 作者: Nakai;K.;Tanaka;T.;Murai;T.;Ohguro;N.;Tano;Y.;Miyasaka;M.
• 通讯作者: M.

CD43 collaborates with P-selectin glycoprotein ligand-1 to mediate E-selectin-dependent T cell migration into inflamed skin

• 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

Nepmucin, a novel HEV sialomucin, mediates L-selectin-dependent lymphocyte rolling and promotes lymphocyte adhesion under flow.

• DOI: 10.1084/jem.20052543
• 发表时间: 2006-06-12
• 期刊: The Journal of experimental medicine
• 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

CXCL13 is an arrest chemokine for B cells in high endothelial venules

• DOI: 10.1182/blood-2005-01-0133
• 发表时间: 2005-10-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Kanemitsu, N;Ebisuno, Y;Miyasaka, M
• 通讯作者: Miyasaka, M