Impaired cytolytic activity of asthma-associated natural killer cells is linked to dysregulated transcriptional program in energy metabolism.
Impaired cytolytic activity of asthma-associated natural killer cells is linked to dysregulated transcriptional program in energy metabolism.
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哮喘相关自然杀伤细胞的细胞溶解活性受损与能量代谢中的转录程序失调有关。
DOI：
10.1016/j.molimm.2018.08.015
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发表时间：
2018
影响因子：
3.6
通讯作者：
Wan Xiaochun
中科院分区：
文献类型：
--
作者：
Wu Haisi;Bi Jiacheng;Wu Gaohui;Zheng Chaoyue;Lu Zhen;Cui Lulu;Wan Xiaochun
自然杀伤（NK）细胞是先天性淋巴细胞的细胞毒性亚群，在宿主防御肿瘤和感染中发挥重要作用，然而，其在慢性疾病中通常功能受损。特应性疾病，如过敏性哮喘，其特征在于2型免疫反应，通常与慢性炎症有关。哮喘相关的免疫环境是否影响NK细胞的细胞溶解功能尚未阐明。在此，将人NK细胞系YTS暴露于来自健康供体或哮喘患者的血清，以分析其细胞溶解功能。我们发现，与正常血清相比，哮喘患者血清降低了YTS细胞对Raji人B淋巴母细胞的细胞溶解活性。这些YTS细胞的溶细胞活性的损害伴随着脱粒电位降低，与Raji细胞的结合形成减弱，以及刺激后ERK磷酸化的过早终止。同时，哮喘患者血清暴露后，YTS细胞的凋亡或细胞死亡并没有增加。重要的是，哮喘相关的YTS NK细胞的细胞溶解活性的这种损害伴随着参与氧化磷酸化的异常富集的基因。总之，这些结果表明，哮喘患者的血清直接抑制NK细胞的细胞溶解功能，可能通过NK细胞中的能量代谢失调。
Natural killer (NK) cells are a cytotoxic subset of the innate lymphoid cells, playing essential roles in host defense against tumors and infections, which, however, are usually functionally compromised in chronic diseases. Atopic diseases, such as allergic asthma, characterized by type 2 immune responses, are usually associated with chronic inflammations. Whether asthma -associated immune environment affects the cytolytic function of NK cells has not been elucidated. Here, YTS, a human NK cell line, was exposed to serum from healthy donors or asthma patients for analysis of its cytolytic function. We found that, serum from asthma patients reduced the cytolytic activity of YTS cells against Raji human B lymphoblasts, in comparison with normal serum. The impairment of cytolytic activity of these YTS cells was accompanied with decreased degranulation potentials, weakened conjugation formation with Raji cells, and premature termination of ERK phosphorylation upon stimulation. Meanwhile, apoptosis or cell death of YTS cells was not increased after exposure to serum from asthma patients. Importantly, such impairment of cytolytic activity of asthma -associated YTS NK cells was accompanied with aberrantly enriched genes involved in oxidative phosphorylation. Taken together, these results demonstrate that the serum of asthma patients directly suppresses the cytolytic function of NK cells, possibly through dysregulation of energy metabolism in NK cells.