Role of IL-25 on Eosinophils in the Initiation of Th2 Responses in Allergic Asthma.
Role of IL-25 on Eosinophils in the Initiation of Th2 Responses in Allergic Asthma.
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IL-25 对嗜酸性粒细胞在过敏性哮喘中 Th2 反应启动中的作用
DOI：
10.3389/fimmu.2022.842500
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发表时间：
2022
影响因子：
7.3
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中科院分区：
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背景嗜酸性粒细胞作为次级抗原呈递细胞（APC）刺激Th细胞对抗原的应答。IL-25在过敏性哮喘中的嗜酸性粒细胞活化中起重要作用。IL-25对树突状细胞的经典APC功能的作用已经阐明。然而，IL-25是否促进嗜酸性粒细胞抗原呈递尚不清楚。目的探讨白细胞介素25（IL-25）对嗜酸性粒细胞抗原提呈功能的影响及其相关机制。方法将过敏性哮喘患者的嗜酸性粒细胞与IL-25和HDM共同培养，检测共刺激分子的表达。患者嗜酸性粒细胞和自体幼稚CD 4 + T细胞在同一培养系统中的共培养旨在探索嗜酸性粒细胞是否具有响应于IL-25接合而促进Th细胞分化的能力。在哮喘小鼠模型中，将IL-25-/-小鼠暴露于HDM以研究IL-25在致敏阶段对嗜酸性粒细胞的影响。评价IL-25对嗜酸性粒细胞摄取抗原的能力的影响。将小鼠骨髓来源的嗜酸性粒细胞（BmEOS）与在HDM和IL-25刺激下从脾脏中分选的幼稚CD 4 +T细胞共培养，以鉴定T细胞分化。结果IL-25可上调过敏性哮喘患者嗜酸性粒细胞HLA-DR、PD-L1和OX-40 L的表达。IL-25和HDM共致敏的嗜酸性粒细胞促进Th 2分化。在小鼠模型中，IL-25-/-小鼠在早期致敏阶段经历了受抑制的过敏性肺部炎症和减少的嗜酸性粒细胞募集和抗原摄取能力。在体外，IL-25促进嗜酸性粒细胞的抗原摄取。在BmEOS和幼稚CD 4 +T细胞共培养中，IL-25增加了CD 4 + Th 2细胞的比例，这在单独的CD 4 +T细胞培养中是不存在的。结论IL-25可增强嗜酸性粒细胞对抗原的摄取和共刺激分子的表达，从而诱导Th 2启动。
Background Eosinophils act as a secondary antigen-presenting cell (APC) to stimulate Th cell responses against antigens. IL-25 plays a significant role in eosinophil activation in allergic asthma. The role of IL-25 on the classic APC functions of dendritic cells has been elucidated. However, whether IL-25 facilitates eosinophils for antigen presentation is unknown. Objective To elucidate the role of IL-25 on eosinophils antigen presenting function during allergic asthma and its related mechanism. Methods Eosinophils from allergic asthma subjects were cultured with IL-25 and HDM to identify the co-stimulator molecules expression. Co-cultures of patient eosinophils and autologous naïve CD4+ T cells in the same culture system were to explore whether eosinophils had the capacity to promote Th cell differentiation in response to IL-25 engagement. In asthma mouse model, IL-25-/- mice were exposed to HDM to investigate the effect of IL-25 on eosinophils during the sensitization phase. The impact of IL-25 on the capacity for eosinophils taking up antigens was evaluated. Mouse bone marrow derived eosinophils (BmEOS) were co-cultured with naïve CD4+T cells sorted from spleens under HDM and IL-25 stimulation to identify T cell differentiation. Results IL-25 upregulated HLA-DR, PD-L1, and OX-40L expression on eosinophils from allergic asthma patients. IL-25 and HDM co-sensitized eosinophils promoted Th2 differentiation. In mouse model, IL-25-/- mice experienced restrained allergic pulmonary inflammation and reduced eosinophils recruitment and antigen uptake capacity during the early sensitization phase. In vitro, IL-25 promoted antigen uptake by eosinophils. In BmEOS and naïve CD4+T cells co-culture, IL-25 accreted the proportion of CD4+Th2 cells, which was absent in CD4+T cells culture alone. Conclusion Our data identify a novel role of IL-25 in enhancing eosinophils antigen uptake and co-stimulator molecules expression to induce Th2 priming in the context of allergic inflammation.