Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY.
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY
J Immunol. 2021 May 15;206(10):2312-2321. doi: 10.4049/jimmunol.2001354. Epub 2021 May 5.
IL-8 is a potent chemokine that recruits neutrophils and basophils to promote inflammation in many species. IL-8 is produced by many cell types, including monocytes. In this study, we report a novel role for IgE-binding monocytes, a rare peripheral immune cell type, to promote allergic inflammation through IL-8 production in a horse model of natural IgE-mediated allergy. We developed a mAb with confirmed specificity for both recombinant and native equine IL-8 for flow cytometric analysis. Equine IL-8 was produced by CD14/MHC class II/CD16 monocytes, including a subpopulation of IgE-binding monocytes, following stimulation with LPS. In addition, IgE cross-linking induced IL-8 production by both peripheral blood basophils and IgE-binding monocytes. IL-8 production was compared between healthy horses and those with a naturally occurring IgE-mediated skin allergy, hypersensitivity. Allergic horses had significantly higher percentages of IL-8 IgE-binding monocytes after IgE cross-linking. In contrast, frequencies of IL-8 basophils after IgE cross-linking were similar in all horses, regardless of allergic disease, highlighting IgE-binding monocytes as a novel source of IL-8 during allergy. We concluded that IgE-binding monocytes from allergic individuals have an increased capacity for IL-8 production and likely contribute to the recruitment of innate immune cells during IgE-mediated allergy and promotion of inflammation during repeated allergen contact.
白细胞介素-8（IL-8）是一种有效的趋化因子，能募集中性粒细胞和嗜碱性粒细胞，促进多种物种的炎症反应。IL-8 由多种细胞类型产生，包括单核细胞。在这项研究中，我们报告了 IgE 结合单核细胞的一个新作用，这是一种罕见的外周免疫细胞类型，通过在自然 IgE 介导的过敏反应的马模型中产生白细胞介素-8 来促进过敏炎症。我们开发了一种针对重组和天然马白细胞介素-8 均具有确认特异性的 mAb，用于流式细胞术分析。CD14/MHC 类 II/CD16 单核细胞（包括 IgE 结合单核细胞的一个亚群）在 LPS 刺激下产生马白细胞介素-8。此外，IgE 交联诱导外周血嗜碱性粒细胞和 IgE 结合单核细胞产生白细胞介素-8。在 IgE 交联后，比较了健康马和自然发生 IgE 介导的皮肤过敏（超敏反应）马之间的白细胞介素-8 产生情况。IgE 交联后，过敏马的 IL-8 IgE 结合单核细胞的百分比明显更高。相比之下，所有马的 IgE 交联后 IL-8 嗜碱性粒细胞的频率相似，无论是否患有过敏疾病，这突出了 IgE 结合单核细胞作为过敏期间白细胞介素-8 的一个新来源。我们得出结论，来自过敏个体的 IgE 结合单核细胞具有增加的白细胞介素-8 产生能力，并且可能有助于 IgE 介导的过敏期间固有免疫细胞的募集，并促进反复接触过敏原时的炎症。
