Natural killer cells regulate eosinophilic inflammation in chronic rhinosinusitis.
Natural killer cells regulate eosinophilic inflammation in chronic rhinosinusitis.
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DOI：
10.1038/srep27615
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发表时间：
2016-06-08
影响因子：
4.6
通讯作者：
Jang YJ
中科院分区：
文献类型：
--
作者：
Kim JH;Choi GE;Lee BJ;Kwon SW;Lee SH;Kim HS;Jang YJ
嗜酸性粒细胞在包括慢性鼻窦炎（CRS）在内的多种炎症性疾病的发病机制中发挥着重要的病理作用。前列腺素 (PG)，特别是 PGD2 的产生失调，被认为是 CRS 中嗜酸性粒细胞炎症的重要影响因素，主要通过对嗜酸性粒细胞的促炎和趋化作用。在这里，我们提供的证据表明，PGD2 可以通过抑制自然杀伤 (NK) 细胞效应功能和 NK 细胞介导的嗜酸性粒细胞调节来促进嗜酸性粒细胞炎症。与健康对照相比，CRS 患者由 NK 细胞介导的嗜酸性粒细胞凋亡显着减少。这种减少与 NK 细胞功能障碍和嗜酸性粒细胞炎症有关。 CRS患者组织嗜酸性粒细胞与血液嗜酸性粒细胞呈正相关。在 CRS 小鼠模型中，NK 细胞耗竭导致血液嗜酸性粒细胞增多和鼻窦组织中嗜酸性粒细胞炎症加剧。与对照组相比，CRS 患者的 PGD2 及其代谢物增加，但 PGE2 和一组细胞因子（包括 TGF-β）增加。在对照组和 CRS 患者中，NK 细胞的效应器功能受到 PGD2 依赖性而非 PGE2 依赖性途径的有效抑制。因此，我们的结果表明，NK 细胞介导的嗜酸性粒细胞调节减少，可能是通过增加 PGD2 水平来实现的，这是之前未认识到的 CRS 中 PG 失调与嗜酸性粒细胞炎症之间的联系。
Eosinophils play a major pathologic role in the pathogenesis of diverse inflammatory diseases including chronic rhinosinusitis (CRS). Dysregulated production of prostaglandin (PG), particularly PGD2, is considered to be an important contributing factor to eosinophilic inflammation in CRS primarily through proinflammatory and chemotactic effects on eosinophils. Here, we provide evidence that PGD2 can promote eosinophilic inflammation through a suppression of Natural killer (NK) cell effector function and NK cell-mediated eosinophil regulation. Eosinophil apoptosis mediated by NK cells was significantly decreased in CRS patients compared with healthy controls. This decrease was associated with NK cell dysfunction and eosinophilic inflammation. Tissue eosinophils were positively correlated with blood eosinophils in CRS patients. In a murine model of CRS, NK cell depletion caused an exacerbation of blood eosinophilia and eosinophilic inflammation in the sinonasal tissue. PGD2 and its metabolite, but not PGE2 and a panel of cytokines including TGF-β, were increased in CRS patients compared with controls. Effector functions of NK cells were potently suppressed by PGD2-dependent, rather than PGE2-dependent, pathway in controls and CRS patients. Thus, our results suggest decreased NK cell-mediated eosinophil regulation, possibly through an increased level of PGD2, as a previously unrecognized link between PG dysregulation and eosinophilic inflammation in CRS.