Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell trafficking
Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell trafficking
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DOI：
10.1073/pnas.1002747107
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发表时间：
2010-09-14
影响因子：
11.1
通讯作者：
Geha, Raif S.
中科院分区：
文献类型：
--
作者：
Koduru, Suresh;Kumar, Lalit;Geha, Raif S.
含有蛋白 CIP4（Cdc42 相互作用蛋白 4）的 F-BAR 结构域与 Cdc42 和 WASP/N-WASP 相互作用，被认为参与丝状肌动蛋白的组装。尽管 CD40L-CD40 轴完整，CIP4(-/-) 小鼠的 T 和 B 淋巴细胞发育正常，但 T 细胞依赖性抗体产生、IgG 抗体亲和力成熟和生发中心 (GC) 形成受损。 CIP4(-/-)小鼠对半抗原的接触超敏反应(CHS)也受损，并且它们的T细胞未能过继性转移CHS。来自 CIP4(-/-)/OT-II 小鼠的卵清蛋白激活的 CD4(+) 效应 T 细胞向抗原攻击的皮肤迁移很差。活化的CIP4(-/-) T细胞在固定的VCAM-1和ICAM-1上表现出受损的粘附和极化，并且在剪切流条件下在鼠内皮细胞单层上的阻滞和迁移有缺陷。这些结果表明，CIP4 在整合素依赖性 T 细胞依赖性抗体反应和 GC 形成以及整合素介导的效应 T 细胞募集到抗原驱动的免疫反应的皮肤部位中发挥着重要作用。
The F-BAR domain containing protein CIP4 (Cdc42 interacting protein 4) interacts with Cdc42 and WASP/N-WASP and is thought to participate in the assembly of filamentous actin. CIP4(-/-) mice had normal T-and B-lymphocyte development but impaired T cell-dependent antibody production, IgG antibody affinity maturation, and germinal center (GC) formation, despite an intact CD40L-CD40 axis. CIP4(-/-) mice also had impaired contact hypersensitivity (CHS) to haptens, and their T cells failed to adoptively transfer CHS. Ovalbumin-activated CD4(+) effector T cells from CIP4(-/-)/OT-II mice migrated poorly to antigen-challenged skin. Activated CIP4(-/-) T cells exhibited impaired adhesion and polarization on immobilized VCAM-1 and ICAM-1 and defective arrest and transmigration across murine endothelial cell monolayers under shear flow conditions. These results demonstrate an important role for CIP4 in integrin-dependent T cell-dependent antibody responses and GC formation and in integrin-mediated recruitment of effector T cells to cutaneous sites of antigen-driven immune reactions.