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| Item Type: | Article |
|---|---|
| Title: | TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2 |
| Creators Name: | 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 and 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. |
| Keywords: | Apoptosis, Cell Differentiation, Cell Division, Epidermis, Gene Deletion, I-Kappa B Kinase, In Situ Hybridization, In Situ Nick-End Labeling, Inflammation, Keratinocytes, Knockout Mice, Messenger RNA, NF-Kappa B, Protein Serine-Threonine Kinases, Skin Diseases, Tumor Necrosis Factor-alpha, Animals, Mice |
| Source: | Nature |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Volume: | 417 |
| Number: | 6891 |
| Page Range: | 861-6 |
| Date: | 20 June 2002 |
| Additional Information: | Erratum in Nature. 2025 Nov 6. doi: 10.1038/s41586-025-09789-z. |
| Official Publication: | https://doi.org/10.1038/nature00820 |
| PubMed: | View item in PubMed |
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