Dynamic immune cell profiling identified natural killer cell shift as the key event in early allograft dysfunction after liver transplantation.
Di LuXinyu YangLinhui PanZhengxing LianWinyen TanJianyong ZhuoModan YangZuyuan LinQiang WeiJun ChenShushen ZhenXiao XuPublished in: Cell proliferation (2023)
Early allograft dysfunction (EAD) is a life-threatening and fast-developing complication after liver transplantation. The underlying mechanism needs to be better understood, and there has yet to be an efficient therapeutic target. This study retrospectively reviewed 109 patients undergoing liver transplantation, with dynamic profiling of CD3/4/8/16/19/45/56 on the peripheral immune cells (before transplant and 2-4 days after). Altogether, 35 out of the 109 patients developed EAD after liver transplantation. We observed a significant decrease in the natural killer cell proportion (NK cell shift, p = 0.008). The NK cell shift was linearly correlated with cold ischemic time (p = 0.016) and was potentially related to the recipients' outcomes. In mouse models, ischemic/reperfusion (I/R) treatments induced the recruitment of NK cells from peripheral blood into liver tissues. NK cell depletion blocked a series of immune cascades (including CD8+ CD127+ T cells) and inhibited hepatocyte injury effectively in I/R and liver transplantation models. We further found that I/R treatment increased hepatic expression of the ligands for natural killer group 2 member D (NKG2D), a primary activating cell surface receptor in NK cells. Blockade of NKG2D showed a similar protective effect against I/R injury, indicating its role in NK cell activation and the subsequent immunological injury. Our findings built a bridge for the translation from innate immune response to EAD at the bedside. Peripheral NK cell shift is associated with the incidence of EAD after liver transplantation. NKG2D-mediated NK cell activation is a potential therapeutic target.
Keyphrases
- nk cells
- single cell
- peripheral blood
- patients undergoing
- end stage renal disease
- cell surface
- innate immune
- cell therapy
- cerebral ischemia
- chronic kidney disease
- oxidative stress
- ejection fraction
- mouse model
- newly diagnosed
- gene expression
- risk factors
- prognostic factors
- signaling pathway
- risk assessment
- climate change
- acute ischemic stroke
- peritoneal dialysis
- adipose tissue
- bone marrow
- insulin resistance
- patient reported outcomes
- combination therapy
- high glucose
- patient reported
- diabetic rats
- weight loss