IKKβ Leads to an Inflammatory Skin Disease Resembling Interface Dermatitis

• Published in: Journal of investigative dermatology Vol. 130; no. 6; pp. 1598 - 1610
• Main Authors: Page, Angustias, Navarro, Manuel, Garín, Marina, Pérez, Paloma, Llanos Casanova, M., Moreno, Rodolfo, Jorcano, José L., Cascallana, José L., Bravo, Ana, Ramírez, Angel
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-06-2010; Nature Publishing Group
• Subjects: Biological and medical sciences; Dermatology; Medical sciences; Skin involvement in other diseases. Miscellaneous. General aspects; Skin disease; Dermatology; Dermatitis; Inflammatory disease
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2010.28

IKKβ is a subunit of the IκB kinase (IKK) complex required for NF-κB activation in response to pro-inflammatory signals. NF-κB regulates the expression of many genes involved in inflammation, immunity, and apoptosis, and also controls cell proliferation and differentiation in different tissues; however, its function in skin physiopathology remains controversial. In this study we report the alterations caused by increased IKKβ activity in skin basal cells of transgenic mice. These animals suffered chronic inflammation with abundant macrophages and other CD45+ infiltrating cells in the skin, which resulted in epidermal basal cell injury and degeneration of hair follicles. They showed histological features characteristic of interface dermatitis (ID). This phenotype is accompanied by an increased production of inflammatory cytokines by transgenic keratinocytes. Accordingly, transcriptome studies show upregulation of genes associated with inflammatory responses. The inflammatory phenotype observed as a consequence of IKKβ overexpression is independent of T and B lymphocytes, as it also arises in mice lacking these cell types. In summary, our data indicate the importance of IKKβ in the development of ID and in the homeostasis of stratified epithelia. Our results also support the idea that IKKβ might be a valid therapeutic target for the treatment of skin inflammatory diseases.