2型炎症中负载警报蛋白的细胞外脂滴诱导气道中性粒细胞浸润
2025/01/06
总结：Ⅱ型固有淋巴细胞（ILC2s）通过协调多种效应细胞谱系的复杂网络参与2型炎症，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（重度哮喘的一种有害症状）中的功能尚不清楚。本研究中，我们在过敏小鼠模型支气管肺泡灌洗液（BALF）中观察到依赖于ILC2的中性粒细胞积聚。通过色谱分析和蛋白质组学分析，在肺ILC2s的上清液中鉴定出可诱导中性粒细胞趋化的警报蛋白高迁移率族蛋白B1（HMGB1）。基因干扰ILC2s中Hmgb1基因可减少BALF中的中性粒细胞数量，减轻气道炎症。HMGB1被加载到活化的肺ILC2s释放的脂滴（LD）膜上。ILC2s中LD积累的基因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被表征的细胞外LD介导的免疫信号传递途径，ILC2s通过该途径调节过敏性炎症期间气道中性粒细胞的浸润。
Alarmin-loaded extracellular lipid droplets induce airway neutrophil infiltration during type 2 inflammation
Rao Z, Liu S, Li Z, Wang Q, Gao F, Peng H, Ren D, Zang Y, Li H, Li Y, Hu Q, He D, Xu H. Alarmin-loaded extracellular lipid droplets induce airway neutrophil infiltration during type 2 inflammation. Immunity. 2024 Nov 12;57(11):2514-2529.e7. doi: 10.1016/j.immuni.2024.09.001. Epub 2024 Oct 3. PMID: 39366382.
Summary: 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.
(四川大学华西医院呼吸与危重症医学科 黄彦立1 王霁1 王刚1 译)
(2024 Nov 12;57(11):2514-2529.e7. doi: 10.1016/j.immuni.2024.09.001. Epub 2024 Oct 3. PMID: 39366382.)
(2024 Nov 12;57(11):2514-2529.e7. doi: 10.1016/j.immuni.2024.09.001. Epub 2024 Oct 3. PMID: 39366382.)
Alarmin-loaded extracellular lipid droplets induce airway neutrophil infiltration during type 2 inflammation
Rao Z, Liu S, Li Z, Wang Q, Gao F, Peng H, Ren D, Zang Y, Li H, Li Y, Hu Q, He D, Xu H. Alarmin-loaded extracellular lipid droplets induce airway neutrophil infiltration during type 2 inflammation. Immunity. 2024 Nov 12;57(11):2514-2529.e7. doi: 10.1016/j.immuni.2024.09.001. Epub 2024 Oct 3. PMID: 39366382.
Summary: 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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纵向评估生物制剂对重度哮喘患者糖皮质激素毒性的降低作用
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