Dysregulated skin barrier function in Tmem79 mutant mice promotes IL-17A-dependent spontaneous skin and lung inflammation

Saunders SP, Floudas A, Moran T, Byrne CM, Rooney MD, Fahy CM, Geoghegan JA, Iwakura Y, Fallon PG, Schwartz C (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Allergy Wiley-Blackwell

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.

Authors with CRIS profile

Christian Schwartz Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

J079: Functional impact of PD-L1:PD-1-interactions on diet-induced obesity and dysbiosis Sept. 1, 2019 - Aug. 31, 2022

Involved external institutions

Tokyo University of Science / 東京理科大学 (Tōkyō Rika Daigaku) JP Japan (JP) Trinity College Dublin IE Ireland (IE)

How to cite

APA:

Saunders, S.P., Floudas, A., Moran, T., Byrne, C.M., Rooney, M.D., Fahy, C.M.,... Schwartz, C. (2020). Dysregulated skin barrier function in Tmem79 mutant mice promotes IL-17A-dependent spontaneous skin and lung inflammation. Allergy. https://doi.org/10.1111/all.14488

MLA:

Saunders, Sean P., et al. "Dysregulated skin barrier function in Tmem79 mutant mice promotes IL-17A-dependent spontaneous skin and lung inflammation." Allergy (2020).

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