[HTML][HTML] Crosstalk between keratinocytes and adaptive immune cells in an IκBα protein-mediated inflammatory disease of the skin

B Rebholz, I Haase, B Eckelt, S Paxian, MJ Flaig… - Immunity, 2007 - cell.com
B Rebholz, I Haase, B Eckelt, S Paxian, MJ Flaig, K Ghoreschi, SA Nedospasov
Immunity, 2007cell.com
Inflammatory diseases at epithelial borders develop from aberrant interactions between
resident cells of the tissue and invading immunocytes. Here, we unraveled basic functions of
epithelial cells and immune cells and the sequence of their interactions in an inflammatory
skin disease. Ubiquitous deficiency of the IκBα protein (Ikba Δ/Δ) as well as concomitant
deletion of Ikba specifically in keratinocytes and T cells (Ikba K5Δ/K5Δ lckΔ/lckΔ) resulted in
an inflammatory skin phenotype that involved the epithelial compartment and depended on …
Summary
Inflammatory diseases at epithelial borders develop from aberrant interactions between resident cells of the tissue and invading immunocytes. Here, we unraveled basic functions of epithelial cells and immune cells and the sequence of their interactions in an inflammatory skin disease. Ubiquitous deficiency of the IκBα protein (IkbaΔ) as well as concomitant deletion of Ikba specifically in keratinocytes and T cells (IkbaK5Δ/K5Δ lckΔ/lckΔ) resulted in an inflammatory skin phenotype that involved the epithelial compartment and depended on the presence of lymphocytes as well as tumor necrosis factor and lymphotoxin signaling. In contrast, mice with selective ablation of Ikba in keratinocytes or lymphocytes showed inflammation limited to the dermal compartment or a normal skin phenotype, respectively. Targeted deletion of RelA from epidermal keratinocytes completely rescued the inflammatory skin phenotype of IkbaΔ mice. This finding emphasizes the important role of aberrant NF-κB activation in both keratinocytes and lymphocytes in the development of the observed inflammatory skin changes.
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