Proteomics analysis reveals alterations of NK cells in patients with severe aplastic anemia
Proteomics analysis reveals alterations of NK cells in patients with severe aplastic anemia
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蛋白质组学分析揭示严重再生障碍性贫血患者 NK 细胞的变化
DOI：
10.1111/ijlh.13175
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发表时间：
2020-06-01
影响因子：
3
通讯作者：
Fu Rong
中科院分区：
文献类型：
--
作者：
Liu Hui;Zhang Tian;Fu Rong
重型再生障碍性贫血（SAA）是一种以严重的全血细胞减少和骨髓造血功能衰竭为特征的疾病。自然杀伤（NK）细胞是一类执行杀伤和免疫调节功能的大颗粒淋巴细胞。我们前期的研究表明，NK细胞在SAA中起着“保护”作用，这种作用被削弱了。方法分离SAA患者和正常人外周血NK细胞，提取总蛋白。结果与正常对照组相比，SAA患者NK细胞中有93种蛋白质的表达水平存在显著差异。其中48个蛋白表达上调，包括组蛋白H1.2、组蛋白H1.3、异质核核糖核蛋白A2/B1（hnRNP A2/B1）和干扰素调节因子1（IRF-1）; 45个蛋白表达下调，包括肌动蛋白相关复合物（ARP 2/3）、组蛋白H3、组蛋白H4、磷酸甘油酸激酶1（PGK 1）和talin-1。基因本体论（GO）功能表明，DEPs主要涉及囊泡介导的转运，先天免疫反应和DNA结合。KEGG分析显示3条上调和12条下调途径，其中细胞内吞和FC-γ受体介导的吞噬作用与NK细胞功能关系最为密切。结论本研究首次对SAA患者NK细胞蛋白质组进行了分析，发现了多种参与NK细胞功能障碍的DEPs，为进一步研究SAA患者免疫调节不足提供了潜在靶点。
Introduction Severe aplastic anemia (SAA) is a disease characterized by severe pancytopenia and hematopoietic failure of bone marrow. Natural killer (NK) cells are a class of large granular lymphocytes that perform killing and immunomodulatory functions. Our previous study demonstrated that NK cells played the "protective" role in SAA, which is weakened. However, the mechanism remains unclear.Methods Peripheral blood NK cells from SAA patients and normal controls were sorted and total proteins were extracted. Then, mass spectrometry was performed to screen differentially expressed proteins (DEPs).Results Significant differences in the expression levels of 93 proteins were observed in NK cells of SAA patients compared with normal controls. Among them, 48 were upregulated proteins, including histone H1.2, histone H1.3, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1), and interferon regulatory factor 1 (IRF-1), and 45 were downregulated proteins, including actin-related complex (ARP2/3), histone H3, histone H4, phosphoglycerate kinase 1 (PGK1), talin-1. Gene Ontology (GO) function indicated that the DEPs most involved were vesicle-mediated transport, innate immune response, and DNA binding. KEGG analysis showed 3 upregulated and 12 downregulated pathways, in which cell endocytosis and FC-gamma receptor-mediated phagocytosis were most closely related to NK cell functions.Conclusion Our study is the first analysis of proteomic profile in NK cells in SAA and found many DEPs involving in dysfunction of NK cells, which provides potential targets for deeper research of inadequate immunomodulation.