The interaction of neutrophils with T cells has been the subject of debate and controversies. Previous studies have suggested that neutrophils may suppress or activate T cells. Despite these studies, the interaction between neutrophils and T cells has remained a largely unexplored field. Here, based on our RNA sequencing (RNA-seq) analysis, we found that neutrophils have differential transcriptional and functional profiling depending on the CD4 T-cell count of the HIV-infected individual. In particular, we identified that neutrophils in healthy individuals express surface Galectin-9 (Gal-9), which is down-regulated upon activation, and is consistently down-regulated in HIV-infected individuals. However, down-regulation of Gal-9 was associated with CD4 T-cell count of patients. Unstimulated neutrophils express high levels of surface Gal-9 that is bound to CD44, and, upon stimulation, neutrophils depalmitoylate CD44 and induce its movement out of the lipid raft. This process causes the release of Gal-9 from the surface of neutrophils. In addition, we found that neutrophil-derived exogenous Gal-9 binds to cell surface CD44 on T cells, which promotes LCK activation and subsequently enhances T-cell activation. Furthermore, this process was regulated by glycolysis and can be inhibited by interleukin (IL)-10. Together, our data reveal a novel mechanism of Gal-9 shedding from the surface of neutrophils. This could explain elevated plasma Gal-9 levels in HIV-infected individuals as an underlying mechanism of the well-characterized chronic immune activation in HIV infection. This study provides a novel role for the Gal-9 shedding from neutrophils. We anticipate that our results will spark renewed investigation into the role of neutrophils in T-cell activation in other acute and chronic conditions, as well as improved strategies for modulating Gal-9 shedding.

中文翻译：

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在 HIV 感染期间，中性粒细胞通过从细胞表面调节释放 CD44 结合的半乳糖凝集素 9 来促进 T 细胞活化。

中性粒细胞与 T 细胞的相互作用一直是争论和争议的主题。以前的研究表明，中性粒细胞可能会抑制或激活 T 细胞。尽管有这些研究，中性粒细胞和 T 细胞之间的相互作用仍然是一个很大程度上未开发的领域。在这里，基于我们的 RNA 测序 (RNA-seq) 分析，我们发现中性粒细胞具有不同的转录和功能分析，具体取决于 HIV 感染者的 CD4 T 细胞计数。特别是，我们发现健康个体中的中性粒细胞表达表面半乳糖凝集素 9 (Gal-9)，其在激活时下调，并且在 HIV 感染者中持续下调。然而，Gal-9 的下调与患者的 CD4 T 细胞计数有关。未受刺激的中性粒细胞表达高水平的表面 Gal-9，其与 CD44 结合，并且在受到刺激时，中性粒细胞将 CD44 脱棕榈酰化并诱导其移出脂筏。这个过程会导致中性粒细胞表面释放 Gal-9。此外，我们发现中性粒细胞衍生的外源性 Gal-9 与 T 细胞上的细胞表面 CD44 结合，促进 LCK 活化并随后增强 T 细胞活化。此外，该过程受糖酵解调节，并可被白细胞介素 (IL)-10 抑制。总之，我们的数据揭示了 Gal-9 从中性粒细胞表面脱落的新机制。这可以将 HIV 感染者血浆 Gal-9 水平升高解释为 HIV 感染中充分表征的慢性免疫激活的潜在机制。这项研究为中性粒细胞的 Gal-9 脱落提供了新的作用。我们预计我们的结果将引发对中性粒细胞在其他急性和慢性疾病中 T 细胞活化中的作用的重新研究，以及调节 Gal-9 脱落的改进策略。