Eosinophils become polarized in response to cytokines such IL-5 or eotaxin prior to directional migration. Polarization is preceded by F-actin assembly, but the mechanisms that regulate these events and how the shape change influences cell migration from the peripheral blood into the lung remain unclear. In this study, we show that the prolyl isomerase, Pin1, is required for IL-5-induced Eos polarization and migration. Co-immunoprecipitation and immunofluorescence analysis revealed that Pin1 directly interacts with members of Rho GTPase family. Mouse eosinophils lacking Pin1 or human cells treated with Pin1 inhibitors showed significantly reduced IL-5-induced GTPase activity and cofilin phosphorylation, resulting in reduced F-actin polymerization, cell polarization, and directional migration to chemokines. Our result suggests that Pin1 regulates cytoskeletal re-organization, eosinophil morphology, and cell migration through the modulation of Rho GTPase activity. Targeting Pin1 along with GTPases could provide a new approach to reduce pulmonary Eos accumulation during asthmatic exacerbations.

中文翻译：

---

Pin1 调节 IL-5 诱导的嗜酸性粒细胞极化和迁移


在定向迁移之前，嗜酸性粒细胞响应 IL-5 或嗜酸性粒细胞趋化因子等细胞因子而极化。极化之前是 F-肌动蛋白组装，但调节这些事件的机制以及形状变化如何影响细胞从外周血迁移到肺部仍不清楚。在这项研究中，我们证明脯氨酰异构酶 Pin1 是 IL-5 诱导的 Eos 极化和迁移所必需的。免疫共沉淀和免疫荧光分析表明 Pin1 直接与 Rho GTPase 家族成员相互作用。缺乏 Pin1 的小鼠嗜酸性粒细胞或用 Pin1 抑制剂处理的人类细胞显示出 IL-5 诱导的 GTPase 活性和丝切蛋白磷酸化显着降低，导致 F-肌动蛋白聚合、细胞极化和向趋化因子的定向迁移减少。我们的结果表明 Pin1 通过调节 Rho GTPase 活性来调节细胞骨架重组、嗜酸性粒细胞形态和细胞迁移。以 Pin1 和 GTPases 为靶点可以提供一种新方法来减少哮喘急性发作期间肺部 Eos 的积累。