原標(biāo)題：集落刺激因子1及其受體是治療過敏性哮喘的新靶點(diǎn)
背景：一種針對粘膜免疫早期事件中氣傳過敏原檢測的新方法可能會帶來很大的好處。 CSF1-CSF1R通路在通過激活樹突狀細(xì)胞將過敏原運(yùn)輸?shù)絽^(qū)域淋巴結(jié)中起著關(guān)鍵作用。干預(yù)該途徑可以防止過敏原致敏和隨后的Th2過敏性炎癥。
方法：我們采用了由三種天然過敏原和CSF1R抑制劑包裹納米探針的新型遞送系統(tǒng)組成的慢性哮喘模型。
結(jié)果：氣道上皮細(xì)胞中CSF1的選擇性耗竭可抑制過敏原特異性IgE的產(chǎn)生，從而預(yù)防新的哮喘發(fā)展，并逆轉(zhuǎn)已建立的過敏性肺部炎癥。含有GW2580（一種選擇性的CSF1R抑制劑）的CDPL-GW納米探針對吸入治療和鼻內(nèi)吹入顯示出良好的藥代動(dòng)力學(xué)，這改善了哮喘病理，包括過敏原特異性血清IgE產(chǎn)生，過敏性肺和氣道炎癥以及氣道高反應(yīng)性（AHR）發(fā)生最小的肺部不良反應(yīng)。
結(jié)論：抑制CSF1-CSF1R信號通路可有效抑制在慢性哮喘小鼠模型中對氣傳過敏原的敏感性和隨之而來的過敏性肺部炎癥。CSF1R抑制是治療過敏性哮喘的新靶點(diǎn)。


延伸閱讀
Allergy                                           
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
　　創(chuàng)建過敏性疾病的科研、科普知識交流平臺，為過敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺。