Dysregulated skin barrier function in Tmem79 mutant mice promotes IL‐17A‐dependent spontaneous skin and lung inflammation. Issue 12 (22nd July 2020)

• Record Type: Journal Article
• Authors: Saunders, Sean P.; Floudas, Achilleas; Moran, Tara; Byrne, Ciara M.; Rooney, Michael D.; Fahy, Caoimhe M. R.; Geoghegan, Joan A.; Iwakura, Yoichiro; Fallon, Padraic G.; Schwartz, Christian
• Is Part Of: Allergy. Volume 75:Issue 12(2020)
• Page Start: 3216
• Page End: 3227
• Publication Date: 2020-07-22
• Subjects: cutaneous inflammation -- interleukin‐17A -- lung inflammation -- skin barrier -- Tmem79; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.14488
• Languages: English
• ISSNs: 0105-4538

Abstract

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. Tmem79 ma/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, Tmem79 ma/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 Tmem79 ma/ma mice was analyzed. We further investigated susceptibility to cutaneous Staphylococcus aureus infection. Tmem79 ma/ma were crossed to IL‐17A‐deficient mice to address the contribution of IL‐17A to spontaneous skin and lung disease. Results: Tmem79 ma/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. Abstract : A single mutation in Tmem79 causes a dysregulation of skin barrier integrity, which – with increasing age – lead to the development of spontaneous dermatitis and subsequent lung inflammation. In Tmem79 ma/ma mice, IL‐17A‐producing γδ T cells and Th17 cells infiltrate the skin prior to the occurrence of pulmonary disease. Progression from skin to lung inflammation is dependent on the presence of γδ T cells and IL‐17A. Abbreviation: Tmem79, transmembrane protein 79