Department of Medicine I, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
J Hepatol. 2013 Jan;58(1):112-8. doi: 10.1016/j.jhep.2012.09.008. Epub 2012 Sep 16.
BACKGROUND & AIMS: The liver can mitigate the inflammatory activity of infiltrating T cells by mechanisms that are not entirely clear. Here we investigated the role of liver sinusoidal endothelial cells (LSECs) in regulating the activity of inflammatory CD4 T cells.
Interactions between T helper (Th) 1 or Th17 cells and LSEC were studied by intravital microscopy and by in vitro stimulation assays.
Circulating CD4 T cells established lasting and repeated interactions with liver endothelium in vivo. Stimulation of Th1 and Th17 cells by LSEC greatly inhibited their capacity to secrete interferon-γ or interleukin-17 in vitro; in contrast, stimulation by dendritic cells (DCs) resulted in considerable secretion of both cytokines. Cytokine release by Th1 or Th17 cells seemed to be actively suppressed by LSEC, as indicated by the inhibition of cytokine secretion even in the presence of Th1- and Th17-promoting DC. This inhibition of CD4 T cell effector function seemed to depend on the dominance of inhibitory over activating co-stimulatory signals on LSEC, since (1) cytokine secretion could be restored by increased CD28 co-activation; (2) LSEC from interleukin-10(-/-) mice, which manifest increased activating signals, such as MHC II, and decreased inhibitory signals, such as PD-L1, failed to suppress cytokine secretion; and (3) cytokine secretion by Th1 or Th17 cells that lacked PD-1, the ligand for inhibitory PD-L1, could not be suppressed by LSEC.
LSEC inhibit inflammatory cytokine secretion of Th1 and Th17 effector CD4 T cells in dependence of interleukin-10 and PD-1.
肝脏通过尚未完全阐明的机制来减轻浸润性 T 细胞的炎症活性。在这里，我们研究了肝窦内皮细胞（LSEC）在调节炎症性 CD4 T 细胞活性中的作用。
通过活体显微镜检查和体外刺激实验研究了辅助性 T 细胞（Th）1 或 Th17 细胞与 LSEC 之间的相互作用。
循环 CD4 T 细胞在体内与肝内皮细胞建立了持久和反复的相互作用。LSEC 刺激 Th1 和 Th17 细胞，极大地抑制了它们在体外分泌干扰素-γ或白细胞介素-17 的能力；相比之下，树突状细胞（DC）的刺激导致这两种细胞因子的大量分泌。Th1 或 Th17 细胞的细胞因子释放似乎被 LSEC 主动抑制，这表明即使存在促进 Th1 和 Th17 的 DC，细胞因子的分泌也受到抑制。CD4 T 细胞效应功能的这种抑制似乎取决于 LSEC 上抑制性共刺激信号相对于激活共刺激信号的优势，因为（1）增加 CD28 共激活可以恢复细胞因子的分泌；（2）缺乏白细胞介素-10（IL-10）的 LSEC 表现出增加的激活信号，如 MHC II，以及减少的抑制信号，如 PD-L1，无法抑制细胞因子的分泌；（3）缺乏 PD-1 的 Th1 或 Th17 细胞（PD-L1 的配体）的细胞因子分泌不能被 LSEC 抑制。
LSEC 抑制炎症性 Th1 和 Th17 效应 CD4 T 细胞细胞因子的分泌，这依赖于白细胞介素-10 和 PD-1。
