Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Immunology. 2018 Jun;154(2):309-321. doi: 10.1111/imm.12886. Epub 2018 Feb 2.
The p21-activated kinase 2 (Pak2), an effector molecule of the Rho family GTPases Rac and Cdc42, regulates diverse functions of T cells. Previously, we showed that Pak2 is required for development and maturation of T cells in the thymus, including thymus-derived regulatory T (Treg) cells. However, whether Pak2 is required for the functions of various subsets of peripheral T cells, such as naive CD4 and helper T-cell subsets including Foxp3 Treg cells, is unknown. To determine the role of Pak2 in CD4 T cells in the periphery, we generated inducible Pak2 knockout (KO) mice, in which Pak2 was deleted in CD4 T cells acutely by administration of tamoxifen. Temporal deletion of Pak2 greatly reduced the number of Foxp3 Treg cells, while minimally affecting the homeostasis of naive CD4 T cells. Pak2 was required for proliferation and Foxp3 expression of Foxp3 Treg cells upon T-cell receptor and interleukin-2 stimulation, differentiation of in vitro induced Treg cells, and activation of naive CD4 T cells. Together, Pak2 is essential in maintaining the peripheral Treg cell pool by providing proliferation and maintenance signals to Foxp3 Treg cells.
p21 激活激酶 2（Pak2）是 Rho 家族 GTPases Rac 和 Cdc42 的效应分子，调节 T 细胞的多种功能。先前，我们表明 Pak2 是胸腺中 T 细胞（包括胸腺衍生的调节性 T（Treg）细胞）发育和成熟所必需的。然而，Pak2 是否需要各种外周 T 细胞亚群的功能，例如幼稚 CD4 和辅助性 T 细胞亚群（包括 Foxp3 Treg 细胞），尚不清楚。为了确定 Pak2 在周围 CD4 T 细胞中的作用，我们生成了诱导型 Pak2 敲除（KO）小鼠，其中 Pak2 通过给予他莫昔芬在 CD4 T 细胞中急性缺失。Pak2 的瞬时缺失大大减少了 Foxp3 Treg 细胞的数量，而对幼稚 CD4 T 细胞的稳态影响最小。Pak2 是 T 细胞受体和白细胞介素-2 刺激时 Foxp3 Treg 细胞增殖和 Foxp3 表达、体外诱导的 Treg 细胞分化以及幼稚 CD4 T 细胞激活所必需的。总之，Pak2 通过向 Foxp3 Treg 细胞提供增殖和维持信号来维持外周 Treg 细胞池。
