Immune complexes (ICs) skew immune responses toward either a pro- or anti-inflammatory direction based on the type of stimulation. Immunoglobulin E (IgE) is associated with Th2 immune responses and known to activate innate immune cells. However, roles of antigen (Ag)-specific-IgE ICs in regulating human eosinophil responses remain elusive; therefore, this study builts upon the mechanism of which ovalbumin (Ova)-IgE ICs affects eosinophilic responses utilizing human EoL-1 cell line as a model. Eosinophils are granulocytes functioning through pattern recognition receptors (PRRs) and destructive granule contents in allergic inflammation and parasitic infections. One of the PRRs that eosinophils express is NLRC4, a member of the CARD domain containing nucleotide-binding oligomerization (NOD)-like receptor (NLR) family. Upon recognition of its specific ligand flagellin, NLRC4 inflammasome is formed and leads to the release of interleukin-1β (IL-1β). We exhibited that Ova-IgE ICs induced the NLRC4-inflammasome components, including NLRC4, caspase-1, intracellular IL-1β, and secretion of IL-1β, as well as the granule contents MMP9, TIMP1, and TIMP2 proteins via TLR2 signaling; these responses were suppressed, when NLRC4 inflammasome got actived in the presence of ICs. Furthermore, Ova-IgE ICs induced mRNA expressions of MMP9, TIMP2, and ECP and protein expressions of MMP9 and TIMP2 in EoL-1 through FcɛRII. Interestingly, TLR2 ligand and Ova-IgE ICs costimulation elevated the number of CD63+ cells, a degranulation marker, as compared to the native IgE. Collectively, our findings provide a mechanism for the impacts of Ova-IgE ICs on eosinophilic responses via NLRC4-inflammasome and may help understand eosinophil-associated diseases, including chronic eosinophilic pneumonia, eosinophilic esophagitis, eosinophilic granulomatosis, parasitic infections, allergy, and asthma.

中文翻译：

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IgE 免疫复合物通过 NLRC4 炎症小体减轻嗜酸性粒细胞免疫反应

免疫复合物 (IC) 根据刺激类型将免疫反应偏向促炎或抗炎方向。免疫球蛋白 E (IgE) 与 Th2 免疫反应相关，已知可激活先天免疫细胞。然而，抗原 (Ag) 特异性 IgE IC 在调节人类嗜酸性粒细胞反应中的作用仍然难以捉摸。因此，本研究以卵清蛋白 (Ova)-IgE IC 影响嗜酸性粒细胞反应的机制为基础，利用人 EoL-1 细胞系作为模型。嗜酸性粒细胞是粒细胞，通过模式识别受体（PRR）和过敏性炎症和寄生虫感染中的破坏性颗粒内容物发挥作用。嗜酸性粒细胞表达的 PRR 之一是 NLRC4，它是包含核苷酸结合寡聚化 (NOD) 样受体 (NLR) 家族的 CARD 结构域的成员。在识别其特异性配体鞭毛蛋白后，NLRC4 炎性体形成并导致白介素 1 β (IL-1 β )的释放。我们展示了 Ova-IgE IC 诱导 NLRC4 炎症小体成分，包括 NLRC4、caspase-1、细胞内 IL-1 β和 IL-1 β的分泌，以及通过 TLR2 诱导颗粒含量 MMP9、TIMP1 和 TIMP2 蛋白信号发送；当 NLRC4 炎性体在 IC 存在的情况下被激活时，这些反应就会受到抑制。此外，Ova-IgE IC通过 Fc ɛ RII 诱导 EoL-1 中MMP9、TIMP2和ECP的 mRNA 表达以及 MMP9 和 TIMP2 的蛋白表达。有趣的是，与天然 IgE 相比，TLR2 配体和 Ova-IgE IC 共刺激增加了 CD63+ 细胞（脱粒标记）的数量。总的来说，我们的研究结果提供了 Ova-IgE IC 通过 NLRC4 炎症小体影响嗜酸性粒细胞反应的机制，并可能有助于了解嗜酸性粒细胞相关疾病，包括慢性嗜酸性粒细胞性肺炎、嗜酸性粒细胞性食管炎、嗜酸性肉芽肿病、寄生虫感染、过敏和哮喘。