Epidermal RelA specifically restricts contact allergen-induced inflammation and apoptosis in skin

Strong inhibition of NF-kB signaling in the epidermis results in spontaneous skin inflammation in mice and men. Since there is evidence for linkage between polymorphisms within the NF-kB signaling pathway and human inflammatory skin phenotypes, we asked whether partial functional inhibition of NF-kB signaling in epidermal keratinocytes can modulate clinically relevant skin inflammation. We therefore mutated rela specifically in the epidermis of mice (RelAE-MUT mice). These mice show no inflammatory phenotype. Induction of contact allergy, but not croton oil induced irritant dermatitis, resulted in stronger ear swelling and increased epidermal thickness in RelAE-MUT mice. Both contact allergen and croton oil treatment led to increase expression of calgranulins A and B (S100A8/ A9) in RelAE-MUT mice. Epidermal hyperproliferation in RelAE-MUT mice was non-cell autonomous since cultured primary epidermal keratinocytes from RelAE-MUT mice showed reduced proliferation compared to controls. These results demonstrate that epidermal RelA specifically regulates DTH-induced skin inflammation. In addition, we here describe an essential but non- specific function of RelA in the protection of epidermal keratinocytes from apoptosis. Our study identifies new functions of NF-kB signaling in the epidermis and corroborates a specific role of epidermal keratinocytes in the regulation of skin inflammation Mouse ear was treated with 2,4- Dinitro fluorobenzene and collected after 48 h of treatments. Two wild types and two mutant mice were used.