杭州浙大迪迅生物基因工程有限公司Allergy：集落刺激因子1及其受体是治疗过敏性哮喘的新靶点
发布日期：2020-06-05
原标题：集落刺激因子1及其受体是治疗过敏性哮喘的新靶点
方法：我们采用了由三种天然过敏原和CSF1R抑制剂包裹纳米探针的新型递送系统组成的慢性哮喘模型。
结果：气道上皮细胞中CSF1的选择性耗竭可抑制过敏原特异性IgE的产生，从而预防新的哮喘发展，并逆转已建立的过敏性肺部炎症。含有GW2580（一种选择性的CSF1R抑制剂）的CDPL-GW纳米探针对吸入治疗和鼻内吹入显示出良好的药代动力学，这改善了哮喘病理，包括过敏原特异性血清IgE产生，过敏性肺和气道炎症以及气道高反应性（AHR）发生最小的肺部不良反应。
结论：抑制CSF1-CSF1R信号通路可有效抑制在慢性哮喘小鼠模型中对气传过敏原的敏感性和随之而来的过敏性肺部炎症。CSF1R抑制是治疗过敏性哮喘的新靶点。
延伸阅读
Allergy
DOI: 10.1111/all.14011
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.
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.
First Author:
Hyung‐Geun Moon
Correspondence:
Hyung‐Geun Moon and Gye Young Park,Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago,840 S. Wood St. CSB‐920N, Chicago, IL 60612, USA.
All Authors:
Hyung‐Geun Moon, Seung‐jae Kim, Myoung Kyu Lee, Homan Kang, Hak Soo Choi, Anantha Harijith, Jinhong Ren, Viswanathan Natarajan, John W. Christman, Steven J. Ackerman, Gye Young Park
——浙大迪迅 译
背景：一种针对粘膜免疫早期事件中气传过敏原检测的新方法可能会带来很大的好处。 CSF1-CSF1R通路在通过激活树突状细胞将过敏原运输到区域淋巴结中起着关键作用。干预该途径可以防止过敏原致敏和随后的Th2过敏性炎症。方法：我们采用了由三种天然过敏原和CSF1R抑制剂包裹纳米探针的新型递送系统组成的慢性哮喘模型。
结果：气道上皮细胞中CSF1的选择性耗竭可抑制过敏原特异性IgE的产生，从而预防新的哮喘发展，并逆转已建立的过敏性肺部炎症。含有GW2580（一种选择性的CSF1R抑制剂）的CDPL-GW纳米探针对吸入治疗和鼻内吹入显示出良好的药代动力学，这改善了哮喘病理，包括过敏原特异性血清IgE产生，过敏性肺和气道炎症以及气道高反应性（AHR）发生最小的肺部不良反应。
结论：抑制CSF1-CSF1R信号通路可有效抑制在慢性哮喘小鼠模型中对气传过敏原的敏感性和随之而来的过敏性肺部炎症。CSF1R抑制是治疗过敏性哮喘的新靶点。
延伸阅读
Allergy
[IF:6.048]
Colony‐stimulating factor 1 and its receptor are new potential therapeutic targets for allergic asthma DOI: 10.1111/all.14011
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.
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.
First Author:
Hyung‐Geun Moon
Correspondence:
Hyung‐Geun Moon and Gye Young Park,Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago,840 S. Wood St. CSB‐920N, Chicago, IL 60612, USA.
All Authors:
Hyung‐Geun Moon, Seung‐jae Kim, Myoung Kyu Lee, Homan Kang, Hak Soo Choi, Anantha Harijith, Jinhong Ren, Viswanathan Natarajan, John W. Christman, Steven J. Ackerman, Gye Young Park
2020-06-15 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。
