Tim-3 pathway affects NK cell impairment in patients with active tuberculosis
Tim-3 pathway affects NK cell impairment in patients with active tuberculosis
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Tim-3 通路影响活动性结核病患者 NK 细胞损伤
DOI：
10.1016/j.cyto.2015.05.012
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发表时间：
2015
期刊：
影响因子：
3.8
通讯作者：
Sun Ziyong
中科院分区：
文献类型：
--
作者：
Wang Feng;Hou Hongyan;Wu Shiji;Tang Qing;Huang Min;Yin Botao;Huang Jing;Liu Weiyong;Mao Lie;Lu Yanfang;Sun Ziyong
活动性结核病（TB）患者的NK细胞功能受损，其潜在机制在很大程度上仍然未知。在这项研究中，我们证实了活动性结核病患者NK细胞的活化、细胞因子分泌和脱粒潜力的降低。我们进一步研究了共抑制受体Tim-3是否参与NK细胞的损伤。我们的研究结果表明，在活动性结核病患者的NK细胞上的Tim-3的表达增加。Tim-3表达与IL-12刺激的IFN-γ产生呈负相关。此外，阻断Tim-3途径恢复了IFN-γ分泌和NK细胞的脱粒。阻断该途径还增加了NK细胞对K562靶细胞的细胞毒性，并提高了NK细胞控制单核细胞衍生的巨噬细胞中Mtb生长的能力。在治疗后的TB患者中还观察到NK细胞上的Tim-3表达显著降低。在这项研究中，我们已经确定了Tim-3与结核病患者的NK细胞损伤有关。
Active tuberculosis (TB) patients show impaired NK cell function, and the underlying mechanism remains largely unknown. In this study, we confirmed the decrease in activation, cytokine secretion, and degranulation potential of NK cells in active TB patients. We further investigated whether coinhibitory receptor Tim-3 was involved with impairment of NK cells. Our results revealed that the expression of Tim-3 on NK cells was increased in active TB patients. Tim-3 expression was inversely correlated with IL-12-stimualted IFN-γ production. Moreover, blocking the Tim-3 pathway restored IFN-γ secretion and degranulation of NK cells. Blocking this pathway also increased NK cell cytotoxicity against K562 target cells, and improved the ability of NK cells to control Mtb growth in monocyte-derived macrophages. The Tim-3 expression on NK cells was also observed to be significantly decreased in TB patients post-treatment. In this study, we have identified that Tim-3 is involved with NK cell impairment in TB patients.