Premium
Dysregulated skin barrier function in Tmem79 mutant mice promotes IL‐17A‐dependent spontaneous skin and lung inflammation
Author(s) -
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
Publication year - 2020
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.14488
Subject(s) - inflammation , immunology , atopic dermatitis , medicine , lung
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.