Regulation of integrin-mediated adhesion and immune response by Rap1 and its downstream effector, p30.

Rap1 及其下游效应子 p30 调节整合素介导的粘附和免疫反应。

• 批准号: 15590436
• 负责人: KATAGIRI Koko
• 金额: $ 2.3万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590436/
• 关键词: Rap1; RAPL; Integrin; cell polarization; migration; homing; chemokine; adhesion; 生体内移動; PAPL; Bリンパ球分化; LFA-1; Tリンパ球

Immunosurveillance requires the coordinated regulation of chemokines and adhesion molecules to guide immune cell migration. However, the critical molecule to govern high trafficking capability of immune cells is not clear. We showed that RAPL plays indispensable roles in integrin-mediated adhesion and migration of lymphocytes and dendritic cells. RAPL deficiency causes defective chemokine-triggered lymphocyte adhesion and migration to secondary lymphoid organs, resulting in atrophic lymphoid follicles and deficient marginal zone B cells, concomitant with increased immature B cells in the blood. Furthermore, splenic dendritic cells were diminished and defective in adhesion. Upon activation with inflammatory stimuli, skin and splenic dendritic cells failed to migrate into either the draining lymph nodes or the white pulp of the spleen. Thus, RAPL is a crucial immune cell trafficking regulator essential for immunosurveillance.

免疫监视需要趋化因子和粘附分子的协调调节来引导免疫细胞迁移。然而，控制免疫细胞高运输能力的关键分子尚不清楚。我们发现 RAPL 在整合素介导的淋巴细胞和树突状细胞的粘附和迁移中起着不可或缺的作用。 RAPL 缺陷会导致趋化因子触发的淋巴细胞粘附和迁移到次级淋巴器官的缺陷，导致淋巴滤泡萎缩和边缘区 B 细胞缺陷，同时血液中未成熟 B 细胞增加。此外，脾树突状细胞减少且粘附有缺陷。在炎症刺激激活后，皮肤和脾脏树突状细胞无法迁移到引流淋巴结或脾白髓中。因此，RAPL 是免疫监视所必需的重要免疫细胞运输调节剂。

项目成果

Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow.

• DOI: 10.1083/jcb.200301133
• 发表时间: 2003-04-28
• 期刊: The Journal of cell biology
• 作者: Shimonaka M;Katagiri K;Nakayama T;Fujita N;Tsuruo T;Yoshie O;Kinashi T
• 通讯作者: Kinashi T

臨床免疫

临床免疫学

• 发表时间: 2003
• 作者: Shimonaka M;Katagiri K;Nakayama T;Fujita N;Tsuruo T;Yoshie O;Kinashi.T.;片桐 晃子
• 通讯作者: 片桐 晃子

RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1

• DOI: 10.1038/ni950
• 发表时间: 2003-08-01
• 期刊: NATURE IMMUNOLOGY
• 影响因子: 30.5
• 作者: Katagiri, K;Maeda, A;Kinashi, T
• 通讯作者: Kinashi, T

Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking

• DOI: 10.1038/ni1111
• 发表时间: 2004-10-01
• 期刊: NATURE IMMUNOLOGY
• 影响因子: 30.5
• 作者: Katagiri, K;Ohnishi, N;Kinashi, T
• 通讯作者: Kinashi, T

Rap1-mediated lymphocyte function-associated antigen-1 activation by the T cell antigen receptor is dependent on phospholipase C-gamma1.

Rap1 介导的 T 细胞抗原受体对淋巴细胞功能相关的抗原 1 的激活依赖于磷脂酶 C-gamma1。

• 发表时间: 2004
• 期刊: J Biol.Chem. 275
• 作者: Katagiri;K. et al.
• 通讯作者: K. et al.