原標題：Tmem79突變小鼠皮膚屏障功能失調導致IL-17A依賴性的自發(fā)性皮膚和肺部炎癥
背景：特應性皮炎（AD）與皮膚屏障調節(jié)失調有關，可能會誘發(fā)繼發(fā)性過敏性疾病，例如哮喘。此前有報道稱Tmem79ma/ma小鼠在編碼跨膜蛋白79（或Mattrin）的基因中存在一個與AD有關的突變。由于Tmem79基因突變，這些小鼠的皮膚屏障存在缺陷，并可發(fā)展為自發(fā)性皮膚炎癥。在這項研究中，評估了Tmem79ma/ma小鼠在自發(fā)性皮膚和肺部炎癥發(fā)展中的潛在免疫反應。
方法：分析Tmem79ma/ma小鼠自發(fā)性皮膚和肺部炎癥的發(fā)生。我們進一步調查了皮膚金黃色葡萄球菌感染的易感性。
將Tmem79ma/ma與IL-17A缺陷型小鼠雜交，以探討IL-17A對自發(fā)性皮膚和肺部疾病的影響。
結果：Tmem79ma/ma小鼠發(fā)生IL-17A依賴性自發(fā)性AD樣炎癥，并且對金黃色葡萄球菌感染不敏感。突變小鼠在皮炎發(fā)生后發(fā)展為氣道炎癥。從皮膚疾病到肺部疾病的發(fā)展取決于適應性免疫，Th17和TCRγδT細胞的皮膚擴張促進了這種疾病的發(fā)展。
結論：缺乏Tmem79/Mattrin表達的小鼠皮膚屏障有缺陷。這些小鼠成年后發(fā)展為皮炎，并繼發(fā)肺部炎癥。皮膚和肺部炎癥的發(fā)展是IL-17A依賴性的，并由TCRγδ T細胞介導。


延伸閱讀
Allergy                                                    
Dysregulated skin barrier function in Tmem79 mutant mice promotes IL-17A-dependent spontaneous skin and lung inflammation
DOI: 10.1111/all.14488
Abstract:
Background: Atopic dermatitis (AD) is associated with a dysregulation of the skin barrier and may predispose to the development of secondary allergic conditions, such as asthma. Tmem79ma/ma mice harbor a mutation in the gene encoding Transmembrane Protein 79 (or Mattrin), which has previously been associated with AD. As a result of the Tmem79 gene mutation, these mice have a defective skin barrier and develop spontaneous skin inflammation. In this study, Tmem79ma/ma mice were assessed for the underlying immunological response in the development of spontaneous skin and lung inflammation
.Methods: Development of spontaneous skin and lung inflammation in Tmem79ma/ma mice was analyzed. We further investigated susceptibility to cutaneous Staphylococcus aureus infection. Tmem79ma/ma were crossed to IL-17A-deficient mice to address the contribution of IL-17A to spontaneous skin and lung disease.
Results: Tmem79ma/ma mice developed IL-17A-dependent spontaneous AD-like inflammation and were refractory to S aureus infection. Mutant mice progressed to airway inflammation subsequent to the occurrence of dermatitis. The progression from skin to lung disease is dependent on adaptive immunity and is facilitated by cutaneous expansion of Th17 and TCRγδ T cells.
Conclusion: Mice lacking Tmem79/Mattrin expression have a defective skin barrier. In adulthood, these mice develop dermatitis with secondary progression to lung inflammation. The development of skin and lung inflammation is IL-17A-dependent and mediated by TCRγδ T cells
First Author:
Sean P. Saunders
Correspondence:
Padraic Fallon, School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
All Authors:
Sean P. Saunders, Achilleas Floudas, Tara Moran, Ciara M. Byrne, Michael D. Rooney, Caoimhe M. R. Fahy, Joan A. Geoghegan, Yoichiro Iwakura, Padraic G. Fallon, Christian Schwartz
2020-12-11 Article 
　　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、預防的共享平臺。