Inflammatory cytokines are pivotal to immune responses. Upon cytokine exposure, cells enter an “alert state” that enhances their visibility to the immune system. Here, we identified an alert-state subpopulation of ribosomes defined by the presence of the P-stalk. We show that P-stalk ribosomes (PSRs) are formed in response to cytokines linked to tumor immunity, and this is at least partially mediated by P-stalk phosphorylation. PSRs are involved in the preferential translation of mRNAs vital for the cytokine response via the more efficient translation of transmembrane domains of receptor molecules involved in cytokine-mediated processes. Importantly, loss of the PSR inhibits CD8+ T cell recognition and killing, and inhibitory cytokines like transforming growth factor β (TGF-β) hinder PSR formation, suggesting that the PSR is a central regulatory hub upon which multiple signals converge. Thus, the PSR is an essential mediator of the cellular rewiring that occurs following cytokine exposure via the translational regulation of this process.

中文翻译：

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P 茎核糖体充当细胞因子介导过程的主要调节因子


炎性细胞因子对免疫反应至关重要。暴露于细胞因子后，细胞进入“警觉状态”，从而提高它们对免疫系统的可见性。在这里，我们确定了由 P 茎的存在定义的核糖体的警报状态亚群。我们表明 P 茎核糖体 （PSR） 是在与肿瘤免疫相关的细胞因子下形成的，这至少部分是由 P 茎磷酸化介导的。PSR 通过更有效地翻译参与细胞因子介导过程的受体分子的跨膜结构域，参与对细胞因子反应至关重要的 mRNA 的优先翻译。重要的是，PSR 的缺失会抑制 CD8+ T 细胞的识别和杀伤，而转化生长因子 β （TGF-β） 等抑制性细胞因子会阻碍 PSR 的形成，这表明 PSR 是多个信号汇聚的中心调节枢纽。因此，PSR 是细胞因子暴露后通过该过程的翻译调节发生的细胞重新布线的重要介质。