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肝泡型包虫病感染通过患者体内NKG2A的高表达导致自然杀伤细胞功能下降。

Hepatic alveolar echinococcosis infection induces a decrease in NK cell function through high expression of NKG2A in patients.

作者信息

Abulizi Abuduaini, Tuergan Talaiti, Shalayiadang Paizula, Zhang Chuanshan, Zhang Ruiqing, Jiang Tiemin, Guo Qiang, Wang Hui, Li Liang, Lin Renyong, Shao Yingmei, Aji Tuerganaili

机构信息

Hepatobiliary & Hydatid Disease Department, Digestive & Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, China.

World Health Organization (WHO) Collaborating Center on Prevention and Management of Echinococcosis, Clinical Medicine Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

出版信息

Front Immunol. 2025 May 12;16:1563248. doi: 10.3389/fimmu.2025.1563248. eCollection 2025.

Abstract

UNLABELLED

larval tapeworm infection in humans is considered a serious public health issue. The immune interaction between parasites and their hosts is extremely important. NK cells are known innate immune cells that play important roles during infection and tumour progression. However, the possible role of NK cells in hepatic alveolar echinococcosis is not completely clear. In this study, we investigated the functional decrease in NK cells in hepatic alveolar echinococcosis (AE) patients.

METHODS

Using human liver tissue samples from 10 patients with hepatic AE, flow cytometry was used to detect the expression of NKG2A molecules on the surface of NK cells, and the correlations between NKG2A+ expression and lesion size, alkaline phosphatase (ALP) levels in close lesion tissues (CLTs) and distal lesion tissues (DLTs) in the liver, and the secretion of functional molecules by NKG2A+ NK cells were analysed.

RESULTS

The expression of NKG2A on CD56dim and CD56bright NK cells in DLTs and CLTs revealed that the percentage of NKG2A+CD56dim NK cells in CLTs was significantly greater than that in DLTs. There was a negative correlation between the expression of NKG2A on NK cells in the CLT and alkaline phosphatase. Additionally, we analysed IFN-γ, TNF-α, granzyme B, and perforin production in NK cells. There was a significant reduction in IFN-γ production in CLTs compared with DLTs. There is a negative correlation between IFN-γ production levels and NKG2A expression in NK cells from the CLT. The capacity of NKG2A+ NK cells from CLT regions to produce IFN-γ and granzyme B was also significantly decreased. In contrast, the perforin level produced by NKG2A+ NK cells was much greater than that produced by NKG2A- NK cells. We also analysed the correlation between the ratio of the NKG2A expression area in CLT and DLT tissues and the PET-CT value and found a positive correlation between NKG2A expression and the PET-CT value.

CONCLUSION

The increased expression of NKG2A in NK cells induced a reduction in IFN-γ production, and the increased expression of NKG2A may improve lesion activity and fibrosis, which may be helpful for treating hepatic alveolar echinococcosis via immunity.

摘要

未标记

人体幼虫绦虫感染被视为一个严重的公共卫生问题。寄生虫与其宿主之间的免疫相互作用极为重要。自然杀伤细胞(NK细胞)是已知的固有免疫细胞,在感染和肿瘤进展过程中发挥重要作用。然而,NK细胞在肝泡型包虫病中的可能作用尚不完全清楚。在本研究中,我们调查了肝泡型包虫病(AE)患者NK细胞的功能下降情况。

方法

使用10例肝AE患者的人肝组织样本,采用流式细胞术检测NK细胞表面NKG2A分子的表达,并分析NKG2A+表达与肝脏中病变大小、紧邻病变组织(CLT)和远端病变组织(DLT)中的碱性磷酸酶(ALP)水平之间的相关性,以及NKG2A+NK细胞功能分子的分泌情况。

结果

DLT和CLT中CD56dim和CD56bright NK细胞上NKG2A的表达显示,CLT中NKG2A+CD56dim NK细胞的百分比显著高于DLT。CLT中NK细胞上NKG2A的表达与碱性磷酸酶之间存在负相关。此外,我们分析了NK细胞中干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、颗粒酶B和穿孔素的产生情况。与DLT相比,CLT中IFN-γ的产生显著减少。CLT中NK细胞的IFN-γ产生水平与NKG2A表达之间存在负相关。CLT区域的NKG2A+NK细胞产生IFN-γ和颗粒酶B的能力也显著降低。相比之下,NKG2A+NK细胞产生的穿孔素水平远高于NKG2A-NK细胞产生的穿孔素水平。我们还分析了CLT和DLT组织中NKG2A表达面积的比值与PET-CT值之间的相关性,发现NKG2A表达与PET-CT值之间存在正相关。

结论

NK细胞中NKG2A表达的增加导致IFN-γ产生减少,NKG2A表达的增加可能会改善病变活性和纤维化,这可能有助于通过免疫治疗肝泡型包虫病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844e/12104054/52fb352aa3a0/fimmu-16-1563248-g001.jpg

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