杭州浙大迪迅生物基因工程有限公司Allergy：鼻窦炎鼻息肉源性嗜酸粒细胞的脂质代谢
发布日期：2019-02-20
原标题：慢性鼻窦炎鼻息肉源性嗜酸粒细胞脂肪酸代谢失调
方法：我们建立了一种从嗜酸性鼻窦炎（NP-EOS）患者鼻息肉中分离CD69hi CCR3low CXCR4- siglec-8int 嗜酸粒细胞的方法，并与健康受试者外周血来源的嗜酸粒细胞（PB-EOS）进行脂质组学、蛋白质组学和转录组学的多组学分析，以分析NP-EOS。
结果：脂源性分析显示前列腺素和15-脂氧合酶（15-lox）衍生介质的合成受损，白三烯D4的产生选择性上调。此外，蛋白质组学和转录组学揭示了导致脂质代谢失调的特异性酶（ggt5、dpep2和15-lox）的表达变化。独创性途径分析表明2型细胞因子和模式识别受体通路的重要性。用嗜酸粒细胞激活剂IL-5、GM-CSF和TLR2、NOD2受体激动剂可以模拟观察到脂质代谢变化。
结论：炎性组织源性嗜酸粒细胞具有一种特殊的表型，其脂肪酸代谢失调可作为治疗的靶向，以控制嗜酸粒细胞性炎症疾病。
延伸阅读
Allergy：
[IF:6.048]
Dysregulated fatty acid metabolism in nasal polyp-derived eosinophils from patients with chronic rhinosinusitis
DOI: 10.1111/all.13726
Background:
Eosinophils are multifunctional granulocytes capable of releasing various cytokines, chemokines, and lipid mediators. We previously reported dysregulated fatty acid metabolism in peripheral blood-derived eosinophils from patients with severe asthma.However, functional characteristics of eosinophils present in allergic inflammatory tissues remains largely uncharacterized.
Methods:
We established a method for isolating CD69hi CCR3low CXCR4- siglec-8int eosinophils from nasal polyps of patients with eosinophilic rhinosinusitis (NP-EOS).Multi-omics analysis including lipidomics, proteomics, and transcriptomics was performed to analyze NP-EOS as compared with peripheral blood-derived eosinophils from healthy subjects (PB-EOS).
Results: Lipidomic analysis revealed impaired synthesis of prostaglandins and 15-lipoxygenase (15-LOX)-derived mediators, and selective upregulation of leukotriene D4 production. Furthermore, proteomics and transcriptomics revealed changes in the expression of specific enzymes (GGT5, DPEP2, and 15-LOX) responsible for dysregulated lipid metabolism. Ingenuity pathway analysis indicated the importance of type 2 cytokines and pattern recognition receptor pathways. Stimulation of PB-EOS with eosinophil activators IL-5, GM-CSF, and agonists of TLR2 and NOD2 mimicked the observed changes in lipid metabolism.
Conclusion:
Inflammatory tissue-derived eosinophils possess a specific phenotype with dysregulated fatty acid metabolism that may be targeted therapeutically to control eosinophilic inflammatory diseases.
First Author:
Jun Miyata
Corresponding authorLaboratory for Metabolomics RIKEN Center for Integrative Medical Sciences 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
All Authors:
Jun Miyata, Koichi Fukunaga, Yusuke Kawashima, Takashi Watanabe, Akina Saitoh,Tomomi Hirosaki, Yasutomo Araki, Toru Kikawada, Tomoko Betsuyaku, Osamu Ohara,Makoto Arita
——浙大迪迅 译
背景：嗜酸粒细胞是一种多功能粒细胞，能够释放多种细胞因子、趋化因子和脂质介质。我们以前报道过严重哮喘患者外周血来源的嗜酸粒细胞脂肪酸代谢失调，但是过敏性炎症组织中嗜酸粒细胞的功能特征在很大程度上仍未被检测出来。方法：我们建立了一种从嗜酸性鼻窦炎（NP-EOS）患者鼻息肉中分离CD69hi CCR3low CXCR4- siglec-8int 嗜酸粒细胞的方法，并与健康受试者外周血来源的嗜酸粒细胞（PB-EOS）进行脂质组学、蛋白质组学和转录组学的多组学分析，以分析NP-EOS。
结果：脂源性分析显示前列腺素和15-脂氧合酶（15-lox）衍生介质的合成受损，白三烯D4的产生选择性上调。此外，蛋白质组学和转录组学揭示了导致脂质代谢失调的特异性酶（ggt5、dpep2和15-lox）的表达变化。独创性途径分析表明2型细胞因子和模式识别受体通路的重要性。用嗜酸粒细胞激活剂IL-5、GM-CSF和TLR2、NOD2受体激动剂可以模拟观察到脂质代谢变化。
结论：炎性组织源性嗜酸粒细胞具有一种特殊的表型，其脂肪酸代谢失调可作为治疗的靶向，以控制嗜酸粒细胞性炎症疾病。
延伸阅读
Allergy：
[IF:6.048]
Dysregulated fatty acid metabolism in nasal polyp-derived eosinophils from patients with chronic rhinosinusitis
DOI: 10.1111/all.13726
Background:
Eosinophils are multifunctional granulocytes capable of releasing various cytokines, chemokines, and lipid mediators. We previously reported dysregulated fatty acid metabolism in peripheral blood-derived eosinophils from patients with severe asthma.However, functional characteristics of eosinophils present in allergic inflammatory tissues remains largely uncharacterized.
Methods:
We established a method for isolating CD69hi CCR3low CXCR4- siglec-8int eosinophils from nasal polyps of patients with eosinophilic rhinosinusitis (NP-EOS).Multi-omics analysis including lipidomics, proteomics, and transcriptomics was performed to analyze NP-EOS as compared with peripheral blood-derived eosinophils from healthy subjects (PB-EOS).
Results: Lipidomic analysis revealed impaired synthesis of prostaglandins and 15-lipoxygenase (15-LOX)-derived mediators, and selective upregulation of leukotriene D4 production. Furthermore, proteomics and transcriptomics revealed changes in the expression of specific enzymes (GGT5, DPEP2, and 15-LOX) responsible for dysregulated lipid metabolism. Ingenuity pathway analysis indicated the importance of type 2 cytokines and pattern recognition receptor pathways. Stimulation of PB-EOS with eosinophil activators IL-5, GM-CSF, and agonists of TLR2 and NOD2 mimicked the observed changes in lipid metabolism.
Conclusion:
Inflammatory tissue-derived eosinophils possess a specific phenotype with dysregulated fatty acid metabolism that may be targeted therapeutically to control eosinophilic inflammatory diseases.
First Author:
Jun Miyata
Corresponding authorLaboratory for Metabolomics RIKEN Center for Integrative Medical Sciences 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
All Authors:
Jun Miyata, Koichi Fukunaga, Yusuke Kawashima, Takashi Watanabe, Akina Saitoh,Tomomi Hirosaki, Yasutomo Araki, Toru Kikawada, Tomoko Betsuyaku, Osamu Ohara,Makoto Arita
2019-01-25 Article
创建过敏性疾病的科研、科普知识交流平台，为过敏患者提供专业诊断、治疗、预防的共享平台。
