Table_3_In vitro differentiated human CD4+ T cells produce hepatocyte growth factor.xlsx

Differentiation of naive CD4+ T cells into effector T cells is a dynamic process in which the cells are polarized into T helper (Th) subsets. The subsets largely consist of four fundamental categories: Th1, Th2, Th17, and regulatory T cells. We show that human memory CD4+ T cells can produce hepatocyte growth factor (HGF), a pleiotropic cytokine which can affect several tissue types through signaling by its receptor, c-Met. In vitro differentiation of T cells into Th-like subsets revealed that HGF producing T cells increase under Th1 conditions. Enrichment of HGF producing cells was possible by targeting cells with surface CD30 expression, a marker discovered through single-cell RNA-sequencing. Furthermore, pharmacological inhibition of PI3K or mTOR was found to inhibit HGF mRNA and protein, while an Akt inhibitor was found to increase these levels. The findings suggest that HGF producing T cells could play a role in disease where Th1 are present.

初始CD4+ T细胞向效应T细胞的分化是一个动态过程，该过程中细胞极化为T辅助（T helper, Th）细胞亚群。该亚群主要包含四大基本类别：Th1、Th2、Th17以及调节性T细胞。我们证实，人类记忆性CD4+ T细胞可产生肝细胞生长因子（hepatocyte growth factor, HGF）——一种可通过其受体c-Met介导的信号通路影响多种组织类型的多效性细胞因子。将T细胞体外分化为类Th细胞亚群的实验显示，在Th1极化条件下，产HGF的T细胞比例显著升高。通过靶向表达表面CD30的细胞可实现产HGF细胞的富集，CD30这一标志物是通过单细胞RNA测序（single-cell RNA-sequencing）技术发现的。此外，研究发现，对PI3K或mTOR进行药理学抑制可下调HGF的mRNA与蛋白表达水平，而Akt抑制剂则可提升二者的表达量。本研究结果提示，产HGF的T细胞可能在存在Th1细胞的疾病中发挥潜在作用。