Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan.
Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Japan.
In Vivo. 2022 Nov-Dec;36(6):2604-2614. doi: 10.21873/invivo.12995.
BACKGROUND/AIM: Invariant natural killer T (iNKT) cells are involved in the initiation and resolution of inflammatory responses. We previously reported that activated iNKT cells facilitate liver repair after hepatic ischemia reperfusion (I/R) injury by accelerating macrophage polarization during the early phase of hepatic I/R injury. Upon activation with α-galactosylceramide (α-GalCer), iNKT cell numbers transiently decrease before increasing within 72 h of stimulation. In the present study, we examined the role of expanded hepatic iNKT cells in the late phase of hepatic I/R injury.
iNKT cells were activated by intraperitoneal injection of α-GalCer in male C57/BL6 mice at the induction of hepatic ischemia followed by reperfusion.
Numbers of activated hepatic iNKT cells immediately diminished after hepatic I/R and reached minimal levels at 24 h and 48 h post-reperfusion. Numbers of hepatic iNKT cells then increased at 72 h and 96 h post-reperfusion to levels approximately 2-fold higher than in mice that underwent a sham operation. Liver repair as demonstrated by decreased necrotic area and increased expression of proliferating cell nuclear antigen (PCNA) was enhanced in α-GalCer-treated mice at 96 h post-reperfusion. Interleukin (IL)-13 production by proliferating iNKT cells was observed at 96 h post-reperfusion, which was associated with enhanced liver repair and increased numbers of reparative macrophages.
Repopulation of hepatic iNKT cells promotes liver repair by stimulating macrophage phenotype switching in the late phase of hepatic I/R injury.
背景/目的：固有自然杀伤 T（iNKT）细胞参与炎症反应的启动和解决。我们之前报道过，激活的 iNKT 细胞通过在肝缺血再灌注（I/R）损伤的早期加速巨噬细胞极化，促进肝 I/R 损伤后的肝修复。在与 α-半乳糖神经酰胺（α-GalCer）激活后，iNKT 细胞的数量在刺激后 72 小时内先短暂减少，然后增加。在本研究中，我们研究了扩展的肝 iNKT 细胞在肝 I/R 损伤后期的作用。
在诱导肝缺血后继发再灌注时，通过腹腔注射 α-GalCer 激活雄性 C57/BL6 小鼠的 iNKT 细胞。
肝 I/R 后，活化的肝 iNKT 细胞数量立即减少，并在再灌注后 24 小时和 48 小时达到最低水平。然后，肝 iNKT 细胞的数量在再灌注后 72 小时和 96 小时增加，达到比假手术组高约 2 倍的水平。再灌注后 96 小时，α-GalCer 处理的小鼠肝损伤减轻，增殖细胞核抗原（PCNA）表达增加，表明肝修复增强。再灌注后 96 小时观察到增殖的 iNKT 细胞产生白细胞介素（IL）-13，这与增强的肝修复和修复性巨噬细胞数量增加有关。
肝 iNKT 细胞的再增殖通过刺激巨噬细胞表型在肝 I/R 损伤后期促进肝修复。
