Background

The pathogenesis of airway allergic disorders (AAD) needs to be further investigated. Eosinophils (Eos) are the canonical effector cells in AAD attacks. Bcl2 like protein-12 (Bcl2L12) is an apoptosis inhibitor and an immune regulator. Eos have the defects of apoptosis. This study aims to investigate the role of Bcl2L12 in the AAD pathogenesis by regulating Eo activities.

Methods

Human nasal lavage fluids (NLF) and mouse bronchoalveolar lavage fluids (BALF) was collected. Eos in NLF and BALF were analyzed by flow cytometry. A murine AAD model was developed with ovalbumin as a specific antigen.

Results

We found that Eos isolated from NLF or BALF of AAD subjects expressed high levels of Bcl2L12 and showed defects of apoptosis. The Bcl2L12 expression in Eos was positively correlated with the AAD response. High lipopolysaccharide levels were detected in the AAD airways, that promoted the Bcl2L12 expression in Eos. Bcl2L12 mediated the LPS-induced autocrine eotaxin 1 expression in Eos through activating the MAPK p38/STAT6/NF-κB signal pathway. Depletion of Bcl2L12 in Eos suppressed experimental AAD in mice.

Conclusions

AAD Eos express high levels of Bcl2L12, the latter is associated with AAD response by regulating the autocrine eotaxin 1 in Eos. Depletion of Bcl2L12 in Eos attenuates experimental AAD, suggesting that to suppress the Bcl2L12 Eos has the translational potential in the treatment of AAD.

中文翻译：

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Bcl2 like protine-12 (Bcl2L12) 通过诱导嗜酸性粒细胞中的自分泌嗜酸性粒细胞趋化因子促进实验性气道过敏性炎症

背景

气道过敏性疾病（AAD）的发病机制需要进一步研究。嗜酸性粒细胞 (Eos) 是 AAD 攻击中的典型效应细胞。Bcl2 样蛋白 12 (Bcl2L12) 是一种细胞凋亡抑制剂和免疫调节剂。Eos具有细胞凋亡的缺陷。本研究旨在通过调节 Eo 活性来研究 Bcl2L12 在 AAD 发病机制中的作用。

方法

收集人鼻灌洗液 (NLF) 和小鼠支气管肺泡灌洗液 (BALF)。通过流式细胞术分析 NLF 和 BALF 中的 Eos。用卵清蛋白作为特异性抗原开发了鼠 AAD 模型。

结果

我们发现从 AAD 受试者的 NLF 或 BALF 中分离出的 Eos 表达高水平的 Bcl2L12 并显示出细胞凋亡缺陷。Eos 中 Bcl2L12 的表达与 AAD 反应呈正相关。在 AAD 气道中检测到高脂多糖水平，这促进了 Eos 中 Bcl2L12 的表达。Bcl2L12 通过激活 MAPK p38/STAT6/NF-κB 信号通路介导 LPS 诱导的 Eos 中自分泌嗜酸性粒细胞趋化因子 1 的表达。Eos 中 Bcl2L12 的消耗抑制了小鼠的实验性 AAD。

结论

AAD Eos 表达高水平的 Bcl2L12，后者通过调节 Eos 中的自分泌嗜酸性粒细胞趋化因子 1 与 AAD 反应相关。Eos 中 Bcl2L12 的消耗减弱了实验性 AAD，表明抑制 Bcl2L12 Eos 具有治疗 AAD 的转化潜力。