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

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 I kappa B alpha protein (lkba(Delta/Delta)) as well as concomitant deletion of lkba specifically in keratinocytes and T cells (lkba(K5 Delta/K5 Delta lck Delta/lCk Delta)) 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 lkba in keratinocytes or lymphocytes showed inflammation limited to the dermal compartment or a normal skin phenotype, respectively. Targeted deletion of ReIA from epidermal keratinocytes completely rescued the inflammatory skin phenotype of lkba(Delta/Delta) mice. This finding emphasizes the important role of aberrant NF-kappa B activation in both keratinocytes and lymphocytes in the development of the observed inflammatory skin changes.