Molecular dynamics of chemokine receptors in memory T cells

记忆T细胞趋化因子受体的分子动力学

• 批准号: 16390143
• 负责人: MATSUSHIMA Kouji
• 金额: $ 9.54万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390143/
• 关键词: chemokine; chemokine receptors; immunological synapse; T cell receptor; arthritis; Rap-1; 関節リウマチ

To disclose the novel function of chemokine receptors, the roles of CCR5 and CXCR3 in T cell receptor mediated signaling were in detail examined. The expression of CCR5 was first found to be induced by T cell receptor mediated activation, and CCR5 and its ligand RANTES granules were observed to be accumulated in the immunological synapse. The activation of CCR5 through TCR mediated signaling was proved by bioluminescence resonance energy transfer method (BRET) using CCR5-renilla and GFP-beta-arrestin. Next, The critical role of CCR5 and CXCR3 in T cell memory response was proved by using CCR5 and CXCR3 double knock out mice-derived T lymphocytes. Furthermore, The pivotal role of CCR5 but not CXCR3 in Type-II collagen induced arthritis was established using CCR5, CXCR3 single and double knock out mice. This result indicates that CCR5 could be a novel therapeutic target for rheumatoid arthritis.

为了揭示趋化因子受体的新功能，详细研究了CCR 5和CXCR 3在T细胞受体介导的信号传导中的作用。首次发现CCR 5的表达是由T细胞受体介导的活化诱导的，并且观察到CCR 5及其配体RANTES颗粒在免疫突触中积聚。通过使用CCR 5-海肾和GFP-β-arrestin的生物发光共振能量转移方法（BRET）证实了通过TCR介导的信号传导激活CCR 5。其次，利用CCR 5和CXCR 3双基因敲除小鼠T淋巴细胞，证实了CCR 5和CXCR 3在T细胞记忆应答中的关键作用。此外，使用CCR 5、CXCR 3单基因敲除和双基因敲除小鼠建立了CCR 5而不是CXCR 3在II型胶原诱导的关节炎中的关键作用。这一结果表明，CCR 5可能是类风湿关节炎的一个新的治疗靶点。

项目成果

Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs.

浆细胞样 DC 帮助淋巴结 DC 诱导抗 HSV CTL。

• DOI: 10.1084/jem.20041961
• 发表时间: 2005-08-01
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Yoneyama, H;Matsuno, K;Toda, E;Nishiwaki, T;Matsuo, N;Nakano, A;Narumi, S;Lu, B;Gerard, C;Ishikawa, S;Matsushima, K
• 通讯作者: Matsushima, K

Mobilization of dendritic cell precursors into the circulation by administration of MIP-lalpha in mice.

通过在小鼠中施用MIP-1α将树突细胞前体动员到循环中。

• 发表时间: 2004
• 期刊: J Natl Cancer Inst. 96(3)
• 作者: Zhang Y;et al.
• 通讯作者: et al.

Enhanced natural killer cell binding and activation by low-fucose IgG1 antibody results in potent antibody-dependent cellular cytotoxicity induction at lower antigen density

• DOI: 10.1158/1078-0432.ccr-04-2263
• 发表时间: 2005-03-15
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Niwa, R;Sakurada, M;Shitara, K
• 通讯作者: Shitara, K

Exacerbation of granuloma formation in IL-1 receptor antagonist-deficient mice with impaired denfritic cell maturation associated with Th2 cytokine production.

IL-1 受体拮抗剂缺陷小鼠中肉芽肿形成加剧，其树突细胞成熟受损，与 Th2 细胞因子的产生相关。

• 发表时间: 2005
• 期刊: J Immunol 174(6)
• 作者: Iizasa H;et al.
• 通讯作者: et al.

Plasmacytoid DCs help lymp node DCs to induce anti-HSV CTLs.

浆细胞样 DC 帮助淋巴结 DC 诱导抗 HSV CTL。

• 发表时间: 2005
• 期刊: J Exp Med 202(3)
• 作者: Yoneyama H;et al.
• 通讯作者: et al.