Department of Surgery, Division of Solid Organ Transplantation and Hepatobiliary Surgery, University of Rochester Medical Center, Rochester, NY 14642, USA.
Cell Immunol. 2011;271(2):286-91. doi: 10.1016/j.cellimm.2011.07.006. Epub 2011 Jul 20.
Natural killer (NK) cells are a component of innate immunity against viral infections through their rapid cytotoxic activity and cytokine production. However, intra-hepatic NK cells' ability to respond to virus is still mostly unknown. Our results show that the synthetic dsRNA polyinosinic-polycytidylic acid (poly I:C), a mimic of a common product of viral infections, activates NK cells directly in the context of cytokines found in the liver, i.e.: poly I:C plus inflammatory cytokines (IL-18, IL-12, and IL-2) induced NK cell IFN-γ production and TRAIL expression, and anti-inflammatory cytokines (TGF-β and IL-10) inhibit NK cell IFN-γ production. Neutralization of IFN-γ blocks poly I:C plus inflammatory cytokines-induced NK cell TRAIL expression, suggesting that IFN-γ is an autocrine differentiation factor for these cells. A better understanding of the intra-hepatic NK cell activation against viral infection may help in the design of therapies and vaccines for the control of viral hepatitis.
自然杀伤 (NK) 细胞是通过其快速细胞毒性活性和细胞因子产生来抵抗病毒感染的固有免疫的一部分。然而，肝内 NK 细胞对病毒的反应能力在很大程度上仍不清楚。我们的结果表明，合成的双链 RNA 聚肌苷酸-聚胞苷酸（poly I:C），是病毒感染常见产物的模拟物，可在肝脏中发现的细胞因子的背景下直接激活 NK 细胞，即：poly I:C 加炎症细胞因子（IL-18、IL-12 和 IL-2）诱导 NK 细胞 IFN-γ 产生和 TRAIL 表达，而抗炎细胞因子（TGF-β 和 IL-10）抑制 NK 细胞 IFN-γ 的产生。IFN-γ 的中和阻断了 poly I:C 加炎症细胞因子诱导的 NK 细胞 TRAIL 表达，表明 IFN-γ 是这些细胞的自分泌分化因子。更好地了解针对病毒感染的肝内 NK 细胞激活可能有助于设计治疗和疫苗来控制病毒性肝炎。
