Spontaneous atopic dermatitis in mice with a defective skin barrier is independent of ILC2 and mediated by IL-1β

Journal article

Publication Details

Author(s): Schwartz C, Moran T, Saunders SP, Kaszlikowska A, Floudas A, Bom J, Nunez G, Iwakura Y, O’Neill L, Irvine AD, McKenzie AN, Ogg G, Walsh PT, Demengeot J, Fallon PG
Journal: Allergy
Publication year: 2019
ISSN: 0105-4538


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
) 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
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
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
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.

FAU Authors / FAU Editors

Schwartz, Christian
Infektionsbiologische Abteilung am Mikrobiologischen Institut

External institutions with authors

Children's Health Ireland at Crumlin
Instituto Gulbenkian de Ciência
MRC Laboratory of Molecular Biology
Tokyo University of Science / 東京理科大学 (Tōkyō Rika Daigaku)
Trinity College Dublin
University of Michigan
University of Oxford

How to cite

Schwartz, C., Moran, T., Saunders, S.P., Kaszlikowska, A., Floudas, A., Bom, J.,... Fallon, P.G. (2019). Spontaneous atopic dermatitis in mice with a defective skin barrier is independent of ILC2 and mediated by IL-1β. Allergy. https://dx.doi.org/10.1111/all.13801

Schwartz, Christian, et al. "Spontaneous atopic dermatitis in mice with a defective skin barrier is independent of ILC2 and mediated by IL-1β." Allergy (2019).


Last updated on 2019-23-05 at 14:23