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Thymic stromal lymphopoietin overproduced by keratinocytes in mouse skin aggravates experimental asthma.


ABSTRACT: Atopic dermatitis (AD) is often the initial step in the "atopic march," given that more than half of AD patients with moderate to severe AD develop asthma later in life. Both AD and asthma share a similar "atopy" phenotype that includes T helper type 2 inflammation with eosinophilia and hyper-IgE immunoglobulinemia, but the molecular mechanisms underlying the "atopic march" remain elusive. In the present study, we show that induced expression of thymic stromal lymphopoietin (TSLP) in mouse epidermal keratinocytes upon topical application of MC903 (a low calcemic analogue of vitamin D3) not only triggers AD as we previously reported but also aggravates experimental allergic asthma induced by ovalbumin sensitization and challenge. Our study, which provides a mouse model to study human "atopic march," indicates that keratinocyte-produced TSLP may represent an important factor in the link of atopic dermatitis to asthma.

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC2635832 | biostudies-other | 2009 Feb

REPOSITORIES: biostudies-other

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Thymic stromal lymphopoietin overproduced by keratinocytes in mouse skin aggravates experimental asthma.

Zhang Zhikun Z   Hener Pierre P   Frossard Nelly N   Kato Shigeaki S   Metzger Daniel D   Li Mei M   Chambon Pierre P  

Proceedings of the National Academy of Sciences of the United States of America 20090202 5


Atopic dermatitis (AD) is often the initial step in the "atopic march," given that more than half of AD patients with moderate to severe AD develop asthma later in life. Both AD and asthma share a similar "atopy" phenotype that includes T helper type 2 inflammation with eosinophilia and hyper-IgE immunoglobulinemia, but the molecular mechanisms underlying the "atopic march" remain elusive. In the present study, we show that induced expression of thymic stromal lymphopoietin (TSLP) in mouse epide  ...[more]

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