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

J Immunol. 2015 Mar 15;194(6):2472-6. doi: 10.4049/jimmunol.1402608. Epub 2015 Feb 13.

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-κB is a key regulator of TNF production and TNF-induced proinflammatory gene expression, and both the psoriatic transcriptome and genetic susceptibility further implicate NF-κB in psoriasis etiopathology. However, the role of NF-κB in psoriasis remains controversial. We analyzed the function of canonical NF-κB 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-κB in keratinocytes is essential for the maintenance of skin immune homeostasis and is protective against spontaneous dermatitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies, Blocking / immunology
  • Antibodies, Blocking / pharmacology
  • Cells, Cultured
  • Dermatitis / genetics
  • Dermatitis / immunology
  • Dermatitis / metabolism
  • Epidermis / immunology*
  • Epidermis / metabolism
  • Epidermis / pathology
  • Female
  • Flow Cytometry
  • Gene Expression / immunology
  • Homeostasis / drug effects
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Male
  • Mice, Knockout
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-rel / genetics
  • Proto-Oncogene Proteins c-rel / immunology*
  • Proto-Oncogene Proteins c-rel / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / immunology*
  • Skin / metabolism
  • Skin / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / immunology*
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antibodies, Blocking
  • Proto-Oncogene Proteins c-rel
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha