Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
KeyMed Biosciences Inc, Chengdu, Sichuan Province, China.
Invest Ophthalmol Vis Sci. 2023 Jul 3;64(10):30. doi: 10.1167/iovs.64.10.30.
To explore the role of Th2 signaling pathway in allergic conjunctivitis (AC).
Serum Th2 cytokines IL-4 or IL-13 of patients with AC were detected using the Meso scale discovery assay to verify the correlation of Th2 immunity and AC pathogenesis. Wistar Han rats were intraperitoneally and subcutaneously injected with ovalbumin (OVA) to establish an experimental AC model and the Th2 signaling pathway was blocked by an investigational neutralizing antibody (CM310). Serum IgE and OVA-specific IgE were detected by ELISA. Conjunctivitis inflammation, infiltration of eosinophils, and mast cell degranulation were detected by histological examination. Immortalized human conjunctival epithelial cells, a conjunctival epithelial cell line, and peripheral blood mononuclear cells of patients with AC were used as the target cells to study the impact of IL-4 or IL-13 on AC progression. Finally, a STAT6 reporter gene system was constructed using immortalized human conjunctival epithelial cells to confirm whether the downstream signaling pathway activated by IL-4 or IL-13.
Serum IL-4 or IL-13 were increased in patients with AC versus healthy individuals. In an OVA-induced rat experimental AC model, blocking the Th2 signaling pathway with CM310, an investigational neutralizing antibody, alleviated the conjunctival symptoms, and decreased serum IgE, suppressed infiltration of eosinophils and mast cell degranulation. Further, an in vitro model showed CM310 suppressed the secretion of inflammatory cytokine from both immune cells and epithelial cells in both patients peripheral blood mononuclear cells and cell line.
Blocking Th2 signaling pathway alleviates the clinical symptoms and inflammation in AC.
探讨 Th2 信号通路在过敏性结膜炎（AC）中的作用。
采用 Meso scale discovery assay 检测 AC 患者血清 Th2 细胞因子 IL-4 或 IL-13，验证 Th2 免疫与 AC 发病机制的相关性。采用卵清蛋白（OVA）对 Wistar Han 大鼠进行腹腔和皮下注射，建立实验性 AC 模型，并采用研究性中和抗体（CM310）阻断 Th2 信号通路。通过 ELISA 检测血清 IgE 和 OVA 特异性 IgE。通过组织学检查检测结膜炎炎症、嗜酸性粒细胞浸润和肥大细胞脱颗粒。将永生化人结膜上皮细胞、结膜上皮细胞系和 AC 患者外周血单个核细胞作为靶细胞，研究 IL-4 或 IL-13 对 AC 进展的影响。最后，使用永生化人结膜上皮细胞构建 STAT6 报告基因系统，以确认 IL-4 或 IL-13 激活的下游信号通路。
与健康个体相比，AC 患者血清中 IL-4 或 IL-13 增加。在 OVA 诱导的大鼠实验性 AC 模型中，用 CM310（一种研究性中和抗体）阻断 Th2 信号通路可缓解结膜症状，降低血清 IgE，抑制嗜酸性粒细胞浸润和肥大细胞脱颗粒。此外，体外模型显示 CM310 可抑制患者外周血单个核细胞和细胞系中免疫细胞和上皮细胞分泌炎性细胞因子。
阻断 Th2 信号通路可缓解 AC 的临床症状和炎症。
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