Pim2 negatively regulates T-cell immune responses through modulating autophagy
Journal of Immunology(2023)
摘要
Abstract Pim kinases affect cell survival, cell proliferation, transcriptional activation, and protein translation by phosphorylating various target substrates. We previously showed that Pim2 plays a distinct role from Pim1 and Pim3, and negatively regulates T-cell allogeneic response and anti-tumor immunity. Pim2 was reported to promote the induction of autophagy in cancer cells, a cellular process that critically impacts T-cell effector function, survival and memory formation. We hypothesize that Pim2 constrains T-cell immune responses through modulating autophagy. Using western blot and electron microscopy, we evaluated the effect of Pim2 on autophagic flux in resting and activated T cells. Pim2 deficiency in T cells attenuated LC3 lipidation, P62 degradation as well as autophagosome formation, suggesting that Pim2 facilitates autophagy in T cells. Mechanistically, Pim2 directly bound with P62 and loss of Pim2 led to accumulation of P62 which further blocked autophagic flux in T cells. Furthermore, augmentation of autophagy via overexpressing Atg5 or metformin treatment reduced effector cytokine production in Pim2-deficient T cells in vitroand reversed the heightened ability of Pim2-deficient T cells for inducing graft-versus-host disease and for controlling breast cancer growth in vivo. Taken together, Pim2 is a key promotor of autophagy in T cells and targeting Pim2 to suppress autophagy may represent a promising strategy to improve T-cell effector function in cancer immunotherapy. The work was supported by NIH grants: R01 CA258440 and R21 CA263140.
更多查看译文
关键词
autophagy,pim2,immune responses,t-cell
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要