自然杀伤细胞(NK细胞)是一种能够通过直接溶解和细胞因子产生来控制肿瘤和病毒感染的淋巴细胞。尽管T细胞和NK细胞都会在受影响的组织中扩增和积累，但是NK细胞扩增在肿瘤和病毒控制中的作用尚不明确。在这里，我们展示了RNA结合蛋白HuR的转录后调控对于NK细胞扩增是必需的，而不会对效应功能产生负面影响。HuR缺陷NK细胞在有丝分裂阶段存在缺陷，包括Ska2的表达和可变剪接减少，Ska2是纺锤体和着丝粒复合体的组成成分。HuR依赖的NK细胞扩增有助于长期巨细胞病毒感染的控制，并在两个独立的肿瘤模型中促进皮下肿瘤的控制，但对于肿瘤的转移并不起作用。这些结果表明，HuR通过转录后调控特异性地影响NK细胞扩增，该扩增对于控制长期病毒感染和实体肿瘤至关重要，但不适用于急性感染或肿瘤转移，这突显了与抗原特异性T细胞控制的基本区别。© 2023 Piersma等。

Natural killer (NK) cells are lymphocytes capable of controlling tumors and virus infections through direct lysis and cytokine production. While both T and NK cells expand and accumulate in affected tissues, the role of NK cell expansion in tumor and viral control is not well understood. Here, we show that posttranscriptional regulation by the RNA-binding protein HuR is essential for NK cell expansion without negatively affecting effector functions. HuR-deficient NK cells displayed defects in the metaphase of the cell cycle, including decreased expression and alternative splicing of Ska2, a component of the spindle and kinetochore complex. HuR-dependent NK cell expansion contributed to long-term cytomegalovirus control and facilitated control of subcutaneous tumors but not tumor metastases in two independent tumor models. These results show that posttranscriptional regulation by HuR specifically affects NK cell expansion, which is required for the control of long-term virus infection and solid tumors, but not acute infection or tumor metastases, highlighting fundamental differences with antigen-specific T cell control.© 2023 Piersma et al.