Wnt 信号抑制 CTL 记忆编程。
Wnt signaling inhibits CTL memory programming.
机构信息
Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742 USA.
出版信息
Mol Immunol. 2013 Dec;56(4):423-33. doi: 10.1016/j.molimm.2013.06.008. Epub 2013 Aug 1.
Induction of functional CTLs is one of the major goals for vaccine development and cancer therapy. Inflammatory cytokines are critical for memory CTL generation. Wnt signaling is important for CTL priming and memory formation, but its role in cytokine-driven memory CTL programming is unclear. We found that wnt signaling inhibited IL-12-driven CTL activation and memory programming. This impaired memory CTL programming was attributed to up-regulation of eomes and down-regulation of T-bet. Wnt signaling suppressed the mTOR pathway during CTL activation, which was different to its effects on other cell types. Interestingly, the impaired memory CTL programming by wnt was partially rescued by mTOR inhibitor rapamycin. In conclusion, we found that crosstalk between wnt and the IL-12 signaling inhibits T-bet and mTOR pathways and impairs memory programming which can be recovered in part by rapamycin. In addition, direct inhibition of wnt signaling during CTL activation does not affect CTL memory programming. Therefore, wnt signaling may serve as a new tool for CTL manipulation in autoimmune diseases and immune therapy for certain cancers.
诱导功能性 CTL 是疫苗开发和癌症治疗的主要目标之一。炎症细胞因子对于记忆 CTL 的产生至关重要。Wnt 信号通路对于 CTL 的初始激活和记忆形成很重要，但它在细胞因子驱动的记忆 CTL 编程中的作用尚不清楚。我们发现，Wnt 信号抑制了 IL-12 驱动的 CTL 激活和记忆编程。这种记忆 CTL 编程的受损归因于 eomes 的上调和 T-bet 的下调。Wnt 信号在 CTL 激活过程中抑制了 mTOR 通路，这与它对其他细胞类型的作用不同。有趣的是，mTOR 抑制剂雷帕霉素部分挽救了 wnt 引起的记忆 CTL 编程受损。总之，我们发现 wnt 和 IL-12 信号之间的串扰抑制了 T-bet 和 mTOR 通路，并损害了记忆编程，雷帕霉素可以部分恢复这一过程。此外，CTL 激活过程中 wnt 信号的直接抑制不会影响 CTL 记忆编程。因此，Wnt 信号可能成为自身免疫性疾病和某些癌症的免疫治疗中 CTL 操纵的新工具。
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