Cutting edge: NF-?B p65 and c-Rel control epidermal development and immune homeostasis in the skin.

ABSTRACT: Psoriasis is an inflammatory skin disease in which activated immune cells and the proinflammatory cytokine TNF are well-known mediators of pathogenesis. The transcription factor NF-?B is a key regulator of TNF production and TNF-induced proinflammatory gene expression, and both the psoriatic transcriptome and genetic susceptibility further implicate NF-?B in psoriasis etiopathology. However, the role of NF-?B in psoriasis remains controversial. We analyzed the function of canonical NF-?B in the epidermis using CRE-mediated deletion of p65 and c-Rel in keratinocytes. In contrast to animals lacking p65 or c-Rel alone, mice lacking both subunits developed severe dermatitis after birth. Consistent with its partial histological similarity to human psoriasis, this condition could be prevented by anti-TNF treatment. Moreover, regulatory T cells in lesional skin played an important role in disease remission. Our results demonstrate that canonical NF-?B in keratinocytes is essential for the maintenance of skin immune homeostasis and is protective against spontaneous dermatitis.

SUBMITTER: Grinberg-Bleyer Y 

PROVIDER: S-EPMC4355158 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature