杭州浙大迪迅生物基因工程有限公司Allergy：巨噬细胞源性的颗粒蛋白前体促进过敏原诱导的气道炎症
发布日期：2020-06-19
原标题：巨噬细胞源性的颗粒蛋白前体促进过敏原诱导的气道炎症
方法：对屋尘螨过敏原致敏小鼠气道PGRN和2型细胞因子的产生进行了检测，并用巨噬细胞、气道上皮细胞和NKT细胞系研究这些分子的主要细胞来源。通过评估支气管肺泡灌洗液中细胞因子水平和组织病理学，阐明PGRN在巨噬细胞源性PGRN缺乏小鼠和NKT细胞敲除小鼠哮喘模型过敏性气道炎症中的作用。本研究还在小鼠模型中加入了重组PGRN，以确认PGRN在过敏性气道炎症中的作用。
结果：在暴露于过敏原的气道中，PGRN的产生先于其他细胞因子，主要来自巨噬细胞。PGRN诱导NKT细胞中IL-4和IL-13的产生以及气道上皮细胞中IL-33和TSLP的产生。在NKT缺陷小鼠中，PGRN诱导的Th2细胞因子产生被抑制。最后，在暴露于过敏原的PGRN缺乏的小鼠中，过敏性炎症显著减弱，但是在致敏期间加入重组PGRN后炎症恢复。
结论：在致敏早期，气道中巨噬细胞源性PGRN的存在可能对于启动Th2免疫反应以及通过诱导NKT和气道上皮细胞中2型细胞因子的产生引起过敏性气道炎症途径至关重要。
延伸阅读
Allergy
DOI: 10.1111/all.14009
Abstract:
Background: Progranulin (PGRN), mainly produced by immune and epithelial cells, has been known to be involved in the development of various inflammatory diseases. However, the function of PGRN in allergic airway inflammation has not been clearly elucidated, we investigated the role of PGRN in allergic airway inflammation.
Methods: Production of PGRN and various type 2 cytokines were evaluated in mouse airways exposed to house dust mite allergen and main cellular sources of these molecules were investigated using in macrophage, airway epithelial cell, and NKT cell lines. We elucidated the role of PGRN in allergic airway inflammation in mouse models of asthma using macrophage derived PGRN-deficient mice and NKT cell knock out mice by evaluating cytokine levels in bronchoalveolar lavage fluids and histopathology. We also supplemented recombinant PGRN in the mouse models to confirm the role of PGRN in allergic airway inflammation.
Results: PGRN production preceded other cytokines, mainly from macrophages, in the airway exposed to allergen. PGRN induced IL-4 and IL-13 production in NKT cells and IL-33 and TSLP in airway epithelial cells. PGRN induced Th2 cytokine production was abolished in NKT-deficient mice. Finally, allergic inflammation was significantly attenuated in allergen-exposed PGRNdeficient mice, but inflammation was restored when recombinant PGRN was supplemented during the allergen sensitization period.
Conclusion: The presence of macrophage-derived PGRN in airways in the early sensitization period may be critical for mounting a Th2 immune response and for following an allergic airway inflammation pathway via induction of type 2 cytokine production in NKT and airway epithelial cells.
First Author:
Jun-Pyo Choi
Correspondence:
Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
All Authors:
Jun-Pyo Choi, So Young Park, Keun-Ai Moon, Eun Hee Ha, Yeon Duk Woo, Doo Hyun Chung, Hyouk-Soo Kwon, Tae-Bum Kim, Hae-Sim Park, Hee-Bom Moon, Woo-Jung Song and You Sook Cho
——浙大迪迅 译
背景：颗粒前体蛋白（Progranulin，PGRN）主要由免疫细胞和上皮细胞产生，参与多种炎症性疾病的发生发展。然而，PGRN在过敏性气道炎症中的作用尚不清楚，本研究主要研究了PGRN在过敏性气道炎症中的作用。方法：对屋尘螨过敏原致敏小鼠气道PGRN和2型细胞因子的产生进行了检测，并用巨噬细胞、气道上皮细胞和NKT细胞系研究这些分子的主要细胞来源。通过评估支气管肺泡灌洗液中细胞因子水平和组织病理学，阐明PGRN在巨噬细胞源性PGRN缺乏小鼠和NKT细胞敲除小鼠哮喘模型过敏性气道炎症中的作用。本研究还在小鼠模型中加入了重组PGRN，以确认PGRN在过敏性气道炎症中的作用。
结果：在暴露于过敏原的气道中，PGRN的产生先于其他细胞因子，主要来自巨噬细胞。PGRN诱导NKT细胞中IL-4和IL-13的产生以及气道上皮细胞中IL-33和TSLP的产生。在NKT缺陷小鼠中，PGRN诱导的Th2细胞因子产生被抑制。最后，在暴露于过敏原的PGRN缺乏的小鼠中，过敏性炎症显著减弱，但是在致敏期间加入重组PGRN后炎症恢复。
结论：在致敏早期，气道中巨噬细胞源性PGRN的存在可能对于启动Th2免疫反应以及通过诱导NKT和气道上皮细胞中2型细胞因子的产生引起过敏性气道炎症途径至关重要。
延伸阅读
Allergy
[IF:6.048]
Early pubertal maturation and risk of childhood asthma: A mendelian randomization and longitudinal studyDOI: 10.1111/all.14009
Abstract:
Background: Progranulin (PGRN), mainly produced by immune and epithelial cells, has been known to be involved in the development of various inflammatory diseases. However, the function of PGRN in allergic airway inflammation has not been clearly elucidated, we investigated the role of PGRN in allergic airway inflammation.
Methods: Production of PGRN and various type 2 cytokines were evaluated in mouse airways exposed to house dust mite allergen and main cellular sources of these molecules were investigated using in macrophage, airway epithelial cell, and NKT cell lines. We elucidated the role of PGRN in allergic airway inflammation in mouse models of asthma using macrophage derived PGRN-deficient mice and NKT cell knock out mice by evaluating cytokine levels in bronchoalveolar lavage fluids and histopathology. We also supplemented recombinant PGRN in the mouse models to confirm the role of PGRN in allergic airway inflammation.
Results: PGRN production preceded other cytokines, mainly from macrophages, in the airway exposed to allergen. PGRN induced IL-4 and IL-13 production in NKT cells and IL-33 and TSLP in airway epithelial cells. PGRN induced Th2 cytokine production was abolished in NKT-deficient mice. Finally, allergic inflammation was significantly attenuated in allergen-exposed PGRNdeficient mice, but inflammation was restored when recombinant PGRN was supplemented during the allergen sensitization period.
Conclusion: The presence of macrophage-derived PGRN in airways in the early sensitization period may be critical for mounting a Th2 immune response and for following an allergic airway inflammation pathway via induction of type 2 cytokine production in NKT and airway epithelial cells.
First Author:
Jun-Pyo Choi
Correspondence:
Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
All Authors:
Jun-Pyo Choi, So Young Park, Keun-Ai Moon, Eun Hee Ha, Yeon Duk Woo, Doo Hyun Chung, Hyouk-Soo Kwon, Tae-Bum Kim, Hae-Sim Park, Hee-Bom Moon, Woo-Jung Song and You Sook Cho
2020-06-19 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。
