Group 2 innate lymphoid cells (ILC2s) play a crucial role in allergic diseases by coordinating a complex network of various effector cell lineages involved in type 2 inflammation. However, their function in regulating airway neutrophil infiltration, a deleterious symptom of severe asthma, remains unknown. Here, we observed ILC2-dependent neutrophil accumulation in the bronchoalveolar lavage fluid (BALF) of allergic mouse models. Chromatography followed by proteomics analysis identified the alarmin high mobility group box-1 (HMGB1) in the supernatant of lung ILC2s initiated neutrophil chemotaxis. Genetic perturbation of Hmgb1 in ILC2s reduced BALF neutrophil numbers and alleviated airway inflammation. HMGB1 was loaded onto the membrane of lipid droplets (LDs) released from activated lung ILC2s. Genetic inhibition of LD accumulation in ILC2s significantly decreased extracellular HMGB1 abundance and BALF neutrophil infiltration. These findings unveil a previously uncharacterized extracellular LD-mediated immune signaling delivery pathway by which ILC2s regulate airway neutrophil infiltration during allergic inflammation.

中文翻译：

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在 2 型炎症期间，载有 Alarmin 的细胞外脂滴诱导气道中性粒细胞浸润


第 2 组先天淋巴细胞 （ILC2） 通过协调参与 2 型炎症的各种效应细胞谱系的复杂网络，在过敏性疾病中起着至关重要的作用。然而，它们在调节气道中性粒细胞浸润（严重哮喘的有害症状）的功能仍然未知。在这里，我们观察到 ILC2 依赖性中性粒细胞在过敏小鼠模型的支气管肺泡灌洗液 （BALF） 中积累。色谱分析后蛋白质组学分析确定了肺 ILC2 上清液中 alarmin 高迁移率组 box-1 （HMGB1） 引发的中性粒细胞趋化性。ILC2 中 Hmgb1 的遗传扰动减少了 BALF 中性粒细胞的数量并减轻了气道炎症。HMGB1 被加载到活化的肺 ILC2 释放的脂滴 （LDs） 膜上。ILC2s 中 LD 积累的遗传抑制显著降低了细胞外 HMGB1 丰度和 BALF 中性粒细胞浸润。这些发现揭示了一种以前未表征的细胞外 LD 介导的免疫信号传递途径，ILC2 通过该途径调节过敏性炎症期间气道中性粒细胞浸润。