Allergen-Dependent Differences in ILC2s Frequencies in Patients With Allergic Rhinitis.
Allergen-Dependent Differences in ILC2s Frequencies in Patients With Allergic Rhinitis.
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DOI：
10.4168/aair.2016.8.3.216
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
Zhang L
中科院分区：
文献类型：
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作者：
Fan D;Wang X;Wang M;Wang Y;Zhang L;Li Y;Fan E;Cao F;Van Crombruggen K;Zhang L
第 2 组先天淋巴细胞 (ILC2) 是一种新型谱系阴性细胞群，通过响应 IL-25 和 IL-33 刺激产生关键的 Th2 型细胞因子 IL-5 和 IL-13 来诱导先天 2 型反应。过敏性鼻炎 (AR) 患者外周血中 ILC2 的积累存在争议； ILC2在AR免疫发病机制中的确切作用仍不清楚。我们研究了 ILC2 在对不同过敏原敏感的表型 AR 中的作用。对 7 名健康对照 (HC)、9 名对屋尘螨 (HDM) 单敏的患者和 8 名对艾蒿单敏的患者的外周血进行流式细胞术分析，以量化 ILC2 频率。从 HDM-AR 和艾蒿-AR 患者中分离外周血单核细胞 (PBMC)，并使用荧光激活细胞分选仪 (FACS) 分离 Lineage- 和 Lineage+ 细胞。使用 Milliplex 磁珠试剂盒评估体外用 IL-25 和/或 IL-33 与 IL-2 联合刺激的 PBMC 以及 Lineage- 和 Lineage+ 细胞上清液中的 IL-5 和 IL-13 水平。与艾蒿-AR患者和HC相比，HDM-AR患者的ILC2百分比显着升高，而艾蒿-AR患者和HC之间没有发现显着差异。与艾蒿-AR患者的PBMC相比，IL-33±IL-25加IL-2在HDM-AR患者的PBMC中诱导显着更多的IL-5和IL-13释放。与艾蒿-AR 患者的 PBMC 相比，IL-25 加 IL-2 还诱导 HDM-AR 患者的 PBMC 中 IL-13 的释放显着增加。与Lineage+细胞相比，IL-33和/或IL-25与IL-2组合的刺激还诱导Lineage-细胞释放显着更多的IL-5和IL-13。对 HDM 或艾草过敏原敏感的 AR 患者在 ILC2 频率上具有不同的表型和功能特征。 ILC2 在 HDM-AR 的发展过程中介导主要的 2 型免疫，可能是一个潜在的治疗靶点。
Group 2 innate lymphoid cells (ILC2s) are a novel population of lineage-negative cells that induce innate type 2 responses by producing the critical Th2-type cytokines IL-5 and IL-13 in response to IL-25 and IL-33 stimulation. ILC2s accumulation in the peripheral blood of patients with allergic rhinitis (AR) is controversial; the precise role of ILC2s in the immunopathogenesis of AR is still not clear. We investigated the role of ILC2s in phenotypic AR sensitized to distinct allergens. Flow cytometric analysis of the peripheral blood of 7 healthy controls (HCs), 9 patients monosensitized to house dust mite (HDM), and 8 patients monosensitized to mugwort was performed to quantify ILC2s frequency. Peripheral blood mononuclear cells (PBMCs) were isolated from HDM-AR and mugwort-AR patients, and Lineage- and Lineage+ cells were separated using a fluorescence-activated cell sorter (FACS). IL-5 and IL-13 levels in the supernatants of PBMCs, and Lineage- and Lineage+ cells stimulated with IL-25 and/or IL-33 combined with IL-2 in vitro were assessed using the Milliplex magnetic bead kit. The percentage of ILC2s was significantly elevated in HDM-AR patients compared to mugwort-AR patients and HCs, while no significant difference was found between mugwort-AR patients and HCs. IL-33±IL-25 plus IL-2 induced a significantly greater release of IL-5 and IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. IL-25 plus IL-2 also induced a significantly greater release of IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. Stimulation with IL-33 and/or IL-25 combined with IL-2 also induced a significantly greater IL-5 and IL-13 release from Lineage- cells compared to Lineage+ cells. AR patients sensitized to HDM or mugwort allergen have distinct phenotypic and functional profiles in ILC2s frequencies. ILC2s mediate major type 2 immunity in the development of HDM-AR and may be a potential therapeutic target.