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- Title
TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2.
- Authors
Pasparakis, Manolis; Courtois, Gilles; Hafner, Martin; Schmidt-Supprian, Marc; Nenci, Arianna; Toksoy, Atiye; Krampert, Monika; Goebeler, Matthias; Gillitzer, Reinhard; Israel, Alain; Krieg, Thomas; Rajewsky, Klaus; Haase, Ingo
- Abstract
The I kappa B kinase (IKK), consisting of the IKK1 and IKK2 catalytic subunits and the NEMO (also known as IKK gamma) regulatory subunit, phosphorylates I kappa B proteins, targeting them for degradation and thus inducing activation of NF-kappa B (reviewed in refs 1, 2). IKK2 and NEMO are necessary for NF-kappa B activation through pro-inflammatory signals. IKK1 seems to be dispensable for this function but controls epidermal differentiation independently of NF-kappa B. Previous studies suggested that NF-kappa B has a function in the growth regulation of epidermal keratinocytes. Mice lacking RelB or I kappa B alpha, as well as both mice and humans with heterozygous NEMO mutations, develop skin lesions. However, the function of NF-kappa B in the epidermis remains unclear. Here we used Cre/loxP-mediated gene targeting to investigate the function of IKK2 specifically in epidermal keratinocytes. IKK2 deficiency inhibits NF-kappa B activation, but does not lead to cell-autonomous hyperproliferation or impaired differentiation of keratinocytes. Mice with epidermis-specific deletion of IKK2 develop a severe inflammatory skin disease, which is caused by a tumour necrosis factor-mediated, alpha beta T-cell-independent inflammatory response that develops in the skin shortly after birth. Our results suggest that the critical function of IKK2-mediated NF-kappa B activity in epidermal keratinocytes is to regulate mechanisms that maintain the immune homeostasis of the skin.
- Publication
Nature, 2002, Vol 417, Issue 6891, p861
- ISSN
0028-0836
- Publication type
Journal Article
- DOI
10.1038/nature00820