嗜酸性粒细胞与胸膜巨噬细胞通过12/15-脂氧合酶通路协同调控IL-33诱导的气道炎症
2025/06/27
摘要
背景：脂肪酸代谢通过合成脂质介质在调节气道炎症中起关键作用。我们既往研究发现，12/15-脂氧合酶（12/15-LOX，即Alox15）来源的代谢物可减轻IL-33诱导的小鼠嗜酸性气道炎症，但其细胞来源尚未明确。
方法：为明确相关细胞类型，本研究采用多种细胞类型特异性的条件性12/15-LOX缺陷小鼠模型。
结果：结果显示，嗜酸性粒细胞与胸膜巨噬细胞是表达12/15-LOX的主要细胞类型，其通过该酶活性抑制气道炎症。在炎症肺组织中，嗜酸性粒细胞是12/15-LOX阳性细胞的主要群体。此外，胸膜巨噬细胞是胸腔内12/15-LOX阳性细胞的主要群体，并能在气道炎症发生时迁移至发炎肺组织。
结论：本研究表明，嗜酸性粒细胞与胸膜巨噬细胞通过表达12/15-LOX协同调控嗜酸性气道炎症。靶向这些细胞中的12/15-LOX代谢通路，可能为重症哮喘的治疗提供新策略。
Eosinophils and pleural macrophages counter regulate IL-33-elicited airway inflammation via the 12/15-lipoxygenase pathway
E. Ito, R. Hayashizaki, T. Hosaka, T. Yamane, J. Miyata, Y. Isobe, et al.
Abstract
BACKGROUND: Fatty acid metabolism plays a crucial role in regulating airway inflammation through the synthesis of lipid mediators. We have previously demonstrated that a 12/15-lipoxygenase (12/15-LOX or Alox15)-derived mediator attenuates IL-33-induced eosinophilic airway inflammation in mice. However, the cellular sources of these mediators remain unclear.
METHODS: To identify the cellular sources, we used several cell type-specific conditional 12/15-LOX-deficient mice.
RESULTS:We found that eosinophils and pleural macrophages were the major 12/15-LOX-expressing cell types responsible for attenuating airway inflammation. Eosinophils were the major population of 12/15-LOX-expressing cells found in inflamed lung tissue. In addition, pleural macrophages were the major population of 12/15-LOX-expressing cells in the thoracic cavity and were found to translocate into inflamed lung tissue in response to airway inflammation.
CONCLUSION: This study suggests that eosinophils and pleural macrophages cooperatively regulate eosinophilic airway inflammation via 12/15-LOX expression. Targeting 12/15-LOX metabolism in these cells may offer new therapeutic strategies for severe asthma.
背景：脂肪酸代谢通过合成脂质介质在调节气道炎症中起关键作用。我们既往研究发现，12/15-脂氧合酶（12/15-LOX，即Alox15）来源的代谢物可减轻IL-33诱导的小鼠嗜酸性气道炎症，但其细胞来源尚未明确。
方法：为明确相关细胞类型，本研究采用多种细胞类型特异性的条件性12/15-LOX缺陷小鼠模型。
结果：结果显示，嗜酸性粒细胞与胸膜巨噬细胞是表达12/15-LOX的主要细胞类型，其通过该酶活性抑制气道炎症。在炎症肺组织中，嗜酸性粒细胞是12/15-LOX阳性细胞的主要群体。此外，胸膜巨噬细胞是胸腔内12/15-LOX阳性细胞的主要群体，并能在气道炎症发生时迁移至发炎肺组织。
结论：本研究表明，嗜酸性粒细胞与胸膜巨噬细胞通过表达12/15-LOX协同调控嗜酸性气道炎症。靶向这些细胞中的12/15-LOX代谢通路，可能为重症哮喘的治疗提供新策略。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Frontiers in Immunology 2025 Vol. 16 DOI: ARTN 156567010.3389/fimmu.2025.1565670）
Eosinophils and pleural macrophages counter regulate IL-33-elicited airway inflammation via the 12/15-lipoxygenase pathway
E. Ito, R. Hayashizaki, T. Hosaka, T. Yamane, J. Miyata, Y. Isobe, et al.
Abstract
BACKGROUND: Fatty acid metabolism plays a crucial role in regulating airway inflammation through the synthesis of lipid mediators. We have previously demonstrated that a 12/15-lipoxygenase (12/15-LOX or Alox15)-derived mediator attenuates IL-33-induced eosinophilic airway inflammation in mice. However, the cellular sources of these mediators remain unclear.
METHODS: To identify the cellular sources, we used several cell type-specific conditional 12/15-LOX-deficient mice.
RESULTS:We found that eosinophils and pleural macrophages were the major 12/15-LOX-expressing cell types responsible for attenuating airway inflammation. Eosinophils were the major population of 12/15-LOX-expressing cells found in inflamed lung tissue. In addition, pleural macrophages were the major population of 12/15-LOX-expressing cells in the thoracic cavity and were found to translocate into inflamed lung tissue in response to airway inflammation.
CONCLUSION: This study suggests that eosinophils and pleural macrophages cooperatively regulate eosinophilic airway inflammation via 12/15-LOX expression. Targeting 12/15-LOX metabolism in these cells may offer new therapeutic strategies for severe asthma.
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