Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Front Immunol. 2019 Mar 5;10:370. doi: 10.3389/fimmu.2019.00370. eCollection 2019.
Normal function of the adaptive immune system requires trafficking of T cells between the blood and lymphoid organs. Lymphocyte homing to lymph nodes requires that they cross endothelial barriers present in blood vessels and lymphatics. This multi-step process requires a remodeling of the lymphocyte plasma membrane, which is mediated by the dynamic re-arrangement of the actin cytoskeleton. Pak1 plays a central role in cell morphology, adhesion and migration in various cell types. Here we demonstrate that Pak1 is required for activated CD4 T cell trafficking to lymph nodes. Pak1 deficiency in T cells causes a defect in the transcription of CCR7 and L-selectin, thereby altering lymphocyte trafficking. Additionally, we report an increase in L-selectin shedding in Pak1-deficient T cells, which correlates with a decrease in the recruitment of calmodulin to the cytoplasmic tail of L-selectin during T cell activation. Overall, our findings demonstrate that by regulating the expression of two major lymph node homing molecules, L-selectin and CCR7, Pak1 mediates activated CD4 T cell trafficking.
适应性免疫系统的正常功能需要 T 细胞在血液和淋巴器官之间迁移。淋巴细胞归巢到淋巴结需要它们穿过血管和淋巴管中存在的内皮屏障。这个多步骤过程需要淋巴细胞质膜的重塑，这是由肌动蛋白细胞骨架的动态重排介导的。Pak1 在各种细胞类型的细胞形态、黏附和迁移中起着核心作用。在这里，我们证明了 Pak1 是激活的 CD4 T 细胞向淋巴结迁移所必需的。T 细胞中 Pak1 的缺失导致 CCR7 和 L-选择素的转录缺陷，从而改变了淋巴细胞的迁移。此外，我们报告在 Pak1 缺陷的 T 细胞中 L-选择素脱落增加，这与 T 细胞激活过程中钙调蛋白向 L-选择素胞质尾募集减少相关。总的来说，我们的研究结果表明，Pak1 通过调节两种主要的淋巴结归巢分子 L-选择素和 CCR7 的表达，介导激活的 CD4 T 细胞的迁移。
