期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 34, 页码 13921-13926出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1307321110
关键词
Atopy; natural helper cells; nuocytes
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) [22791093, 23791297, 23249022, 24791183]
- Strategic Program Grant for Research Institute Development in Private Institute from MEXT in Japan
- Research on Measures for Intractable Diseases Project, matching fund subsidy [H23-028]
- Ministry of Health, Labour, and Welfare, Japan
- Grants-in-Aid for Scientific Research [22791093, 24791183, 23791297, 23249022] Funding Source: KAKEN
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-alpha, IFN-gamma, 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.
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