Alarmin-loaded extracellular lipid droplets induce airway neutrophil infiltration during type 2 inflammation

IF 25.5 1区医学 Q1 IMMUNOLOGY

Immunity Pub Date : 2024-10-03 DOI:10.1016/j.immuni.2024.09.001

Zebing Rao, Shaorui Liu, Zhicheng Li, Qiuying Wang, Feng Gao, Han Peng, Deshan Ren, Yang Zang, Hui Li, Yan Li, Qi Hu, Danyang He, Heping Xu

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Abstract

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.

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

第 2 组先天性淋巴细胞（ILC2s）通过协调参与 2 型炎症的各种效应细胞系的复杂网络，在过敏性疾病中发挥着至关重要的作用。然而，它们在调节气道中性粒细胞浸润（严重哮喘的一种有害症状）方面的功能仍然未知。在这里，我们观察到过敏性小鼠模型的支气管肺泡灌洗液（BALF）中存在依赖于 ILC2 的中性粒细胞聚集。通过色谱法和蛋白质组学分析，我们在肺部 ILC2 引发中性粒细胞趋化的上清液中发现了警戒素高迁移率组盒-1（HMGB1）。对 ILC2s 中的 Hmgb1 进行遗传扰乱可减少 BALF 中性粒细胞的数量并减轻气道炎症。活化的肺ILC2释放的脂滴（LD）膜上负载了HMGB1。基因抑制 ILC2s 中 LD 的积累可显著降低细胞外 HMGB1 的丰度和 BALF 中性粒细胞的浸润。这些发现揭示了一种以前未曾描述过的细胞外LD介导的免疫信号传递途径，ILC2通过这种途径在过敏性炎症期间调节气道中性粒细胞的浸润。

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来源期刊

Immunity 医学-免疫学

CiteScore

49.40

自引率

2.20%

发文量

205

审稿时长

6 months

期刊介绍： Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.