集落刺激因子1及其受体是过敏性哮喘的新的潜在治疗靶点
2020/02/11
摘要
背景：一种针对早期粘膜免疫事件的空气变应原传感的新方法可能有更大的益处。CSF1-CSF1R通路在通过激活树突状细胞将过敏原运送到区域淋巴结中起着关键作用。对这一途径的干预可以预防过敏原致敏和随后的Th2过敏性炎症。
目的:为了检测CSF1和CSF1R抑制剂对阻断感应空气变应原的树突状细胞功能的治疗效果。方法:我们采用由由三种天然过敏原和新型CSF1R抑制剂传递系统封装纳米探针诱导的慢性哮喘模型。
结果：气道上皮细胞CSF1的选择性耗竭抑制了过敏原反应性IgE的产生，从而预防了新的哮喘的发展，逆转了已经存在的过敏性肺部炎症。含有GW2580的CDPL-GW纳米探针(一种选择性CSF1R抑制剂)显示出对于吸入和鼻内吹入CDPL-GW纳米探针，存在有利的药代动力学能够改善了哮喘的病理，包括特异性过敏原血清IgE的产生、过敏性肺和气道炎症以及气道高反应性(AHR)，而肺部不良反应最小。
结论:CSF1-CSF1R信号通路的抑制有效地降低了慢性哮喘小鼠模型对空气变应原的敏感性，从而抑制了致敏性肺炎症。抑制CSF1R是治疗过敏性哮喘的一个有前景的新靶点。
Colony stimulating factor 1 and its receptor are new potential therapeutic targets for allergic asthma.
Moon HG, et al. Allergy. 2019 Aug 6.
Abstract
BACKGROUND:A new approach targeting aeroallergen sensing in the early events of mucosal immunity could have greater benefit. The CSF1-CSF1R pathway has a critical role in trafficking allergens to regional lymph nodes through activating dendritic cells. Intervention in this pathway could prevent allergen sensitization and subsequent Th2 allergic inflammation.
OBJECTIVE:To examine the therapeutic effectiveness of CSF1 and CSF1R inhibition for blocking the dendritic cell function of sensing aeroallerens
METHODS: We adopted a model of chronic asthma induced by a panel of three naturally occurring allergens and novel delivery system of CSF1R inhibitor encapsulated nanoprobe
RESULTS: Selective depletion of CSF1 in airway epithelial cells abolished the production of allergen-reactive IgE, resulting in prevention of new asthma development as well as reversal of established allergic lung inflammation. CDPL-GW nanoprobe containing GW2580, a selective CSF1R inhibitor, showed favorable pharmacokinetics for inhalational treatment and intranasal insufflation delivery of CDPL-GW nanoprobe ameliorated asthma pathologies including allergen-specific serum IgE production, allergic lung and airway inflammation and airway hyper-responsiveness (AHR) with minimal pulmonary adverse reaction.
CONCLUSION:The inhibition of the CSF1-CSF1R signaling pathway effectively suppresses sensitization to aeroallergens and consequent allergic lung inflammation in a murine model of chronic asthma. CSF1R inhibition is a promising new target for the treatment of allergic asthma.
背景：一种针对早期粘膜免疫事件的空气变应原传感的新方法可能有更大的益处。CSF1-CSF1R通路在通过激活树突状细胞将过敏原运送到区域淋巴结中起着关键作用。对这一途径的干预可以预防过敏原致敏和随后的Th2过敏性炎症。
目的:为了检测CSF1和CSF1R抑制剂对阻断感应空气变应原的树突状细胞功能的治疗效果。方法:我们采用由由三种天然过敏原和新型CSF1R抑制剂传递系统封装纳米探针诱导的慢性哮喘模型。
结果：气道上皮细胞CSF1的选择性耗竭抑制了过敏原反应性IgE的产生，从而预防了新的哮喘的发展，逆转了已经存在的过敏性肺部炎症。含有GW2580的CDPL-GW纳米探针(一种选择性CSF1R抑制剂)显示出对于吸入和鼻内吹入CDPL-GW纳米探针，存在有利的药代动力学能够改善了哮喘的病理，包括特异性过敏原血清IgE的产生、过敏性肺和气道炎症以及气道高反应性(AHR)，而肺部不良反应最小。
结论:CSF1-CSF1R信号通路的抑制有效地降低了慢性哮喘小鼠模型对空气变应原的敏感性，从而抑制了致敏性肺炎症。抑制CSF1R是治疗过敏性哮喘的一个有前景的新靶点。
（中国医科大学附属第一医院 李文扬 摘译 杨冬 审校）
（Moon HG, et al. Allergy. 2019 Aug 6.）
（Moon HG, et al. Allergy. 2019 Aug 6.）
Colony stimulating factor 1 and its receptor are new potential therapeutic targets for allergic asthma.
Moon HG, et al. Allergy. 2019 Aug 6.
Abstract
BACKGROUND:A new approach targeting aeroallergen sensing in the early events of mucosal immunity could have greater benefit. The CSF1-CSF1R pathway has a critical role in trafficking allergens to regional lymph nodes through activating dendritic cells. Intervention in this pathway could prevent allergen sensitization and subsequent Th2 allergic inflammation.
OBJECTIVE:To examine the therapeutic effectiveness of CSF1 and CSF1R inhibition for blocking the dendritic cell function of sensing aeroallerens
METHODS: We adopted a model of chronic asthma induced by a panel of three naturally occurring allergens and novel delivery system of CSF1R inhibitor encapsulated nanoprobe
RESULTS: Selective depletion of CSF1 in airway epithelial cells abolished the production of allergen-reactive IgE, resulting in prevention of new asthma development as well as reversal of established allergic lung inflammation. CDPL-GW nanoprobe containing GW2580, a selective CSF1R inhibitor, showed favorable pharmacokinetics for inhalational treatment and intranasal insufflation delivery of CDPL-GW nanoprobe ameliorated asthma pathologies including allergen-specific serum IgE production, allergic lung and airway inflammation and airway hyper-responsiveness (AHR) with minimal pulmonary adverse reaction.
CONCLUSION:The inhibition of the CSF1-CSF1R signaling pathway effectively suppresses sensitization to aeroallergens and consequent allergic lung inflammation in a murine model of chronic asthma. CSF1R inhibition is a promising new target for the treatment of allergic asthma.
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人气道上皮细胞外囊泡miRNA特征随哮喘发展改变
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在TH2型低哮喘小鼠模型中，T细胞骨髓IL-10轴调节致病性IFN-γ依赖性免疫
