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@article{faucris.217796192,
abstract = {Background: Atopic dermatitis (AD) is one of the most common skin diseases with a multifactorial etiology. Mutations leading to loss of skin barrier function are associated with the development of AD with group 2 innate lymphoid cells (ILC2) promoting acute skin inflammation. Filaggrin-mutant (Flg
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) mice develop spontaneous skin inflammation accompanied by an increase in skin ILC2 numbers, IL-1β production, and other cytokines recapitulating human AD. Here, we investigated the role of ILC2, effector cytokines, inflammasome activation, and mast cell function on the development of chronic AD-like inflammation in mice. Methods: Mice with a frameshift mutation in the filaggrin gene develop spontaneous dermatitis. Flg
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mice were crossed to cell- or cytokine-deficient mouse strains, or bred under germ-free conditions. Skin inflammation was scored, and microbiome composition was analyzed. Skin protein expression was measured by multiplex immunoassay. Infiltrating cells were analyzed by flow cytometry. Results: Wild-type and Flg
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mice significantly differ in their microbiome composition. Furthermore, mutant mice do not develop skin inflammation under germ-free conditions. ILC2 deficiency did not ameliorate chronic dermatitis in Flg
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mice, which was also independent of IL-4, IL-5, IL-9, IL-13, IL-17A, and IL-22. Inflammation was independent of NLRP3 inflammasome activation but required IL-1β and IL-1R1-signaling. Mechanistically, IL-1β promoted hyperactivation of IL-1R1-expressing mast cells. Treatment with anti-IL-1β-antibody alleviated dermatitis exacerbation, while antibiotic intervention ameliorated dermatitis in neonatal mice but not in adults with established inflammation. Conclusions: In summary, we identified a critical role for the microbiome and IL-1β mediating chronic inflammation in mice with an impaired skin barrier.},
author = {Schwartz, Christian and Moran, Tara and Saunders, Sean P. and Kaszlikowska, Agnieszka and Floudas, Achilleas and Bom, Joana and Nunez, Gabriel and Iwakura, Yoichiro and O’Neill, Luke and Irvine, Alan D. and McKenzie, Andrew N.J. and Ogg, Graham and Walsh, Patrick T. and Demengeot, Jocelyne and Fallon, Padraic G.},
doi = {10.1111/all.13801},
faupublication = {yes},
journal = {Allergy},
keywords = {atopic dermatitis; filaggrin; IL-1β; innate lymphoid cells; microbiome},
note = {CRIS-Team Scopus Importer:2019-05-17},
peerreviewed = {Yes},
title = {{Spontaneous} atopic dermatitis in mice with a defective skin barrier is independent of {ILC2} and mediated by {IL}-1β},
year = {2019}
}