P21‐activated kinase 2 is essential in maintenance of peripheral Foxp3⁺ regulatory T cells

Abstract

SummaryThe 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.

Oncogenes and tumor suppressor genes: functions and roles in cancers

“…119 Ectopic FOXP3 expression inhibits almost all tumor cell types despite the lack of analogous research with the two known X-linked tumor suppressors. [120][121][122][123] Recent anisomycin studies have shown that FOXP3 expression in mice and human tumor cells is therapeutic. 114 Carcinogenesis often involves TSG dysfunction.…”

“…Elegant investigations showed that tumors can become “addicted” to Trp53 (p53) depletion 119 . Ectopic FOXP3 expression inhibits almost all tumor cell types despite the lack of analogous research with the two known X‐linked tumor suppressors 120–123 . Recent anisomycin studies have shown that FOXP3 expression in mice and human tumor cells is therapeutic 114 .…”