Allergy and Immunology Research Project Team, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan; Center for Allergy, Nihon University Itabashi Hospital, Tokyo, Japan; Center for Medical Education, Nihon University School of Medicine, Tokyo, Japan.
Allergy and Immunology Research Project Team, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan; Center for Allergy, Nihon University Itabashi Hospital, Tokyo, Japan; Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
J Allergy Clin Immunol. 2021 May;147(5):1878-1891. doi: 10.1016/j.jaci.2021.01.002. Epub 2021 Jan 17.
Mast cells (MCs) are key regulators of IgE-mediated allergic inflammation. Cell-derived extracellular vesicles (EVs) contain bioactive compounds such as microRNAs. EVs can transfer signals to recipient cells, thus using a novel mechanism of cell-to-cell communication. However, whether MC-derived EVs are involved in FcεRI-mediated allergic inflammation is unclear.
We sought to investigate the effect of EVs derived from FcεRI-aggregated human MCs on the function of human group 2 innate lymphoid cells (ILC2s).
Human cultured MCs were sensitized with and without IgE for 1 hour and then incubated with anti-IgE antibody, IL-33, or medium alone for 24 hours. EVs in the MC supernatant were isolated by using ExoQuick-TC.
Coculture of ILC2s with EVs derived from the FcεRI-aggregated MCs significantly enhanced IL-5 production and sustained upregulation of IL-5 mRNA expression in IL-33-stimulated ILC2s, but IL-13 production and IL-13 mRNA expression were unchanged. miR103a-3p expression was upregulated in IL-33-stimulated ILC2s that had been cocultured with EVs derived from anti-IgE antibody-stimulated MCs. Transduction of an miR103a-3p mimic to ILC2s significantly enhanced IL-5 production by IL-33-stimulated ILC2s. miR103a-3p promoted demethylation of an arginine residue of GATA3 by downregulating protein arginine methyltransferase 5 (PRMT5) mRNA. Reduction of protein arginine methyltransferase 5 expression in ILC2s by using a small interfering RNA technique resulted in upregulation of IL-5 production by IL-33-stimulated ILC2s. Furthermore, the level of miR103a-3p expression was significantly higher in EVs from sera of patients with atopic dermatitis than in EVs from nonatopic healthy control subjects.
Eosinophilic allergic inflammation may be exacerbated owing to ILC2 activation by MC-derived miR103a-3p.
肥大细胞（MCs）是 IgE 介导的过敏炎症的关键调节因子。细胞衍生的细胞外囊泡（EVs）含有生物活性化合物，如 microRNAs。EVs 可以向受体细胞传递信号，从而使用一种新的细胞间通讯机制。然而，MC 衍生的 EV 是否参与 FcεRI 介导的过敏炎症尚不清楚。
我们旨在研究源自 FcεRI 聚集的人类 MC 的 EV 对人类 2 型固有淋巴细胞（ILC2）功能的影响。
用 IgE 致敏和未致敏的人 MC 培养 1 小时，然后用抗 IgE 抗体、IL-33 或培养基单独孵育 24 小时。用 ExoQuick-TC 从 MC 上清液中分离 EV。
ILC2 与源自 FcεRI 聚集的 MC 的 EV 共培养，可显著增强 IL-5 的产生，并在 IL-33 刺激的 ILC2 中持续上调 IL-5 mRNA 表达，但 IL-13 的产生和 IL-13 mRNA 表达不变。miR103a-3p 在与源自抗 IgE 抗体刺激的 MC 的 EV 共培养的 IL-33 刺激的 ILC2 中上调。转导 miR103a-3p 模拟物可显著增强 IL-33 刺激的 ILC2 中的 IL-5 产生。miR103a-3p 通过下调蛋白精氨酸甲基转移酶 5（PRMT5）mRNA 促进 GATA3 精氨酸残基的去甲基化。用小干扰 RNA 技术减少 ILC2 中的蛋白精氨酸甲基转移酶 5 表达，可导致 IL-33 刺激的 ILC2 中 IL-5 的产生上调。此外，特应性皮炎患者血清中的 EV 中 miR103a-3p 的表达水平明显高于非特应性健康对照者的 EV。
由于 MC 衍生的 miR103a-3p 对 ILC2 的激活，嗜酸性过敏炎症可能加剧。
