首都医科大学Dong Zhang等研究人员合作发现，TCRαβ+双阴性T调节细胞通过嘌呤能信号改善肝脏缺血再灌注损伤。这一研究成果于2024年11月28日在线发表在国际学术期刊《科学通报》上。

研究人员表示，肝脏缺血再灌注损伤（HIRI）是肝脏移植和大范围肝脏切除后肝脏损伤的重要原因，且中性粒细胞是HIRI中的关键效应细胞。双阴性T调节细胞（DNT）在免疫系统中日益被认为具有关键的调节功能。DNT是否通过特定的免疫调节机制调节中性粒细胞，如在HIRI中，仍然不完全明确。

研究人员发现小鼠和人类DNT高度表达CD39。CD39能够保护DNT免受细胞外ATP诱导的凋亡，并与CD73共同生成腺苷，从而诱导高水平的中性粒细胞凋亡。此外，细胞外腺苷通过A2AR/pAKT/FOXO1信号通路上调survivin和NKG2D表达，增强DNT的存活和抑制功能。DNT的过继转移通过CD39依赖的方式抑制中性粒细胞，从而改善小鼠的HIRI。

最后，A2ar^-/- DNT的过继转移验证了腺苷/A2AR信号通路在促进DNT存活和免疫调节功能中的重要性，能够保护小鼠免受HIRI的损害。总之，嘌呤能信号在HIRI中对DNT的稳态至关重要。增强CD39或激活A2AR信号通路可能为靶向先天免疫紊乱提供新的治疗策略。

附：英文原文

Title: Purinergic signaling by TCRαβ+ double-negative T regulatory cells ameliorates liver ischemia-reperfusion injury

Author: Simon C. Robson f, Guangyong Sun a b c, Dong Zhang b c d e

Issue&Volume: 2024/11/28

Abstract: Hepatic ischemia-reperfusion injury (HIRI) is an important cause of liver injury following liver transplantation and major resections, and neutrophils are the key effector cells in HIRI. Double-negative T regulatory cells (DNT) are increasingly recognized as having critical regulatory functions in the immune system. Whether DNT expresses distinct immunoregulatory mechanisms to modulate neutrophils, as in HIRI, remains largely unknown. In this study, we found that murine and human DNT highly expressed CD39 that protected DNT from extracellular ATP-induced apoptosis and generated adenosine in tandem with CD73, to induce high levels of neutrophil apoptosis. Furthermore, extracellular adenosine enhanced DNT survival and suppressive function by upregulating survivin and NKG2D expression via the A2AR/pAKT/FOXO1 signaling pathway. Adoptive transfer of DNT ameliorated HIRI in mice through the inhibition of neutrophils in a CD39-dependent manner. Lastly, the adoptive transfer of A2ar-/- DNT validated the importance of adenosine/A2AR signaling, in promoting DNT survival and immunomodulatory function to protect against HIRI in vivo. In conclusion, purinergic signaling is crucial for DNT homeostasis in HIRI. Augmentation of CD39 or activation of A2AR signaling in DNT may provide novel therapeutic strategies to target innate immune disorders.

DOI: 10.1016/j.scib.2024.11.039

Source: https://www.sciencedirect.com/science/article/pii/S2095927324008715