State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100101, China.
Cell Mol Immunol. 2018 Aug;15(8):782-793. doi: 10.1038/cmi.2017.163. Epub 2018 Mar 5.
Neutrophils are involved in the pathogenesis of allergy. However, the contribution of the different functionally polarized neutrophils in allergy needs to be clarified. We sought to define the characteristics of interleukin (IL)-33-induced neutrophils and the involvement of this subset of polarized neutrophils in allergic pathogenesis. Freshly isolated neutrophils were treated with different cytokines and the cytokine expression levels were detected by real-time PCR. The gene expression profile of IL-33-induced neutrophils was determined by microarray assay. Adoptive transfer assay was used to investigate the function of IL-33-induced neutrophils in an ovalbumin (OVA)-induced allergic asthma model. IL-33-treated neutrophils selectively produced IL-4, IL-5, IL-9 and IL-13 (referred as to N(IL-33) cells) and displayed a distinctive gene expression profile in sharp contrast to resting and lipopolysaccharide (LPS)-treated neutrophils. IL-33-induced neutrophils expressed high Levels of IL-1R2 on cell surface, whereas resting and LPS-treated neutrophils did not, indicating IL-1R2 might be used as a biomarker for N(IL-33) cells. Importantly, N(IL-33) neutrophils exist in the lungs of OVA-induced allergic asthma mice. Adoptive transfer of N(IL-33) neutrophils significantly promotes the severity of the lung pathogenesis in this model. IL-33 induces neutrophil polarization through c-Jun N-terminal kinase- and nuclear factor-κB-dependent pathways. A previously unappreciated neutrophil polarization driven by IL-33 with unique cell surface markers and cytokine/chemokine-producing gene profile was defined. The newly identified N(IL-33) subpopulation may have significant contribution to IL-33-related pathogenesis.
中性粒细胞参与过敏反应的发病机制。然而，不同功能极化的中性粒细胞在过敏反应中的贡献尚需阐明。我们试图确定白细胞介素（IL）-33 诱导的中性粒细胞的特征以及这种极化中性粒细胞亚群在过敏发病机制中的作用。通过实时 PCR 检测不同细胞因子处理后中性粒细胞的细胞因子表达水平。通过微阵列分析确定 IL-33 诱导的中性粒细胞的基因表达谱。采用过继转移实验研究 IL-33 诱导的中性粒细胞在卵清蛋白（OVA）诱导的过敏性哮喘模型中的功能。IL-33 处理的中性粒细胞选择性地产生 IL-4、IL-5、IL-9 和 IL-13（称为 N（IL-33）细胞），与静止和脂多糖（LPS）处理的中性粒细胞相比，表现出截然不同的基因表达谱。IL-33 诱导的中性粒细胞表面表达高水平的白细胞介素 1 受体 2（IL-1R2），而静止和 LPS 处理的中性粒细胞则不表达，表明 IL-1R2 可能作为 N（IL-33）细胞的标志物。重要的是，N（IL-33）中性粒细胞存在于 OVA 诱导的过敏性哮喘小鼠的肺部。N（IL-33）中性粒细胞的过继转移显著促进了该模型中肺部发病机制的严重程度。IL-33 通过 c-Jun N 端激酶和核因子-κB 依赖性途径诱导中性粒细胞极化。确定了一种以前未被认识到的由 IL-33 驱动的、具有独特细胞表面标志物和细胞因子/趋化因子产生基因谱的中性粒细胞极化。新鉴定的 N（IL-33）亚群可能对与 IL-33 相关的发病机制有重要贡献。
