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Publication : Retinoid X receptor ablation in adult mouse keratinocytes generates an atopic dermatitis triggered by thymic stromal lymphopoietin.

First Author  Li M Year  2005
Journal  Proc Natl Acad Sci U S A Volume  102
Issue  41 Pages  14795-800
PubMed ID  16199515 Mgi Jnum  J:102470
Mgi Id  MGI:3607639 Doi  10.1073/pnas.0507385102
Citation  Li M, et al. (2005) Retinoid X receptor ablation in adult mouse keratinocytes generates an atopic dermatitis triggered by thymic stromal lymphopoietin. Proc Natl Acad Sci U S A 102(41):14795-800
abstractText  To investigate the role of retinoid X receptors (RXRs) in epidermal homeostasis, we generated RXRalphabeta(ep-/-) somatic mutants in which both RXRalpha and RXRbeta are selectively ablated in epidermal keratinocytes of adult mice. These mice develop a chronic dermatitis mimicking that observed in atopic dermatitis (AD) patients. In addition, they exhibit immunological abnormalities including elevated serum levels of IgE and IgG, associated with blood and tissue eosinophilia, indicating that keratinocyte-selective ablation of RXRs also generates a systemic syndrome similar to that found in AD patients. Furthermore, the profile of increased expression of cytokines and chemokines in skin of keratinocyte-selective RXRalphabeta-ablated mutants was typical of a T helper 2-type inflammation, known to be crucially involved in human AD pathogenesis. Finally, we demonstrate that thymic stromal lymphopoietin, whose expression is rapidly and strongly induced in RXRalphabeta-ablated keratinocytes, plays a key role in initiating the skin and systemic AD-like pathologies.
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