Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice
Edited by Tadamitsu Kishimoto, Immunology Frontier Research Center, Osaka University, Suita, Japan, and approved July 18, 2013 (received for review April 24, 2013)
Abstract
Transgenic mice expressing the mouse interleukin 33 (IL-33) gene driven by a keratin 14 promoter were generated. The skin-selective expression of the IL-33 gene was enhanced, and intense immunofluorescence for IL-33 was evident in the nuclei of the epidermis. Spontaneous itchy dermatitis developed in those mice at 6–8 wk of age in specific pathogen-free conditions. In the lesional skin, the epidermis was thickened and the eosinophils were infiltrated with increased expression of the eosinophil peroxidase and major basic protein genes. Mast cells were also abundant there, and blood histamine and total IgE levels were high. Those phenotypes closely resemble the features of atopic dermatitis. In peripheral blood and lesional skin, IL-5, IL-13, regulated upon activation, normally T-expressed, and presumably secreted (RANTES)/CCL5, and Eotaxin 1/CCL11 were increased, whereas TNF-α, IFN-γ, and thymic stromal lymphopoietin (TSLP) were unaltered. Furthermore, the proportion of group 2 innate lymphoid cells (ILC2s), which produce IL-5, were significantly increased in the lesional skin, peripheral blood, and regional lymph nodes. The dermatitis with eosinophil infiltration was improved by the administration of an anti-IL-5 antibody. These results suggest that the expression of IL-33 in the skin activates an immune response involving ILC2 and that this process might play a crucial role in the pathogenesis of allergic inflammation that is characteristic of atopic dermatitis.
Acknowledgments
We thank Dr. Naoki Takeda and members of the Center for Animal Resources and Development, Kumamoto University, and members of the Institute of Experimental Animal Sciences and the Joint-Use Research Facilities, Hyogo College of Medicine, for their technical assistance. This work was supported in part by Ministry of Education, Culture, Sports, Science and Technology (MEXT) or Japan Society for the Promotion of Science (JSPS) KAKENHI (22791093, 23791297, 23249022, and 24791183) and by a Strategic Program Grant for Research Institute Development in Private Institute from MEXT in Japan, by a grant from the “Research on Measures for Intractable Diseases” Project, matching fund subsidy (H23-028), and by a Health and Labour Sciences Research Grant Adjuvant Database Project from the Ministry of Health, Labour, and Welfare, Japan.
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Published online: August 5, 2013
Published in issue: August 20, 2013
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Acknowledgments
We thank Dr. Naoki Takeda and members of the Center for Animal Resources and Development, Kumamoto University, and members of the Institute of Experimental Animal Sciences and the Joint-Use Research Facilities, Hyogo College of Medicine, for their technical assistance. This work was supported in part by Ministry of Education, Culture, Sports, Science and Technology (MEXT) or Japan Society for the Promotion of Science (JSPS) KAKENHI (22791093, 23791297, 23249022, and 24791183) and by a Strategic Program Grant for Research Institute Development in Private Institute from MEXT in Japan, by a grant from the “Research on Measures for Intractable Diseases” Project, matching fund subsidy (H23-028), and by a Health and Labour Sciences Research Grant Adjuvant Database Project from the Ministry of Health, Labour, and Welfare, Japan.
Notes
*This Direct Submission article had a prearranged editor.
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The authors declare no conflict of interest.
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