title: Cutting edge: NF-κB 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-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.
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors: Yenkel
authors: Y
authors: Grinberg-Bleyer
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors: Teruki
authors: T
authors: Dainichi
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors: Hyunju
authors: H
authors: Oh
authors: Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors: Nicole
authors: N
authors: Heise
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors: Ulf
authors: U
authors: Klein
authors: Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität Munich, Munich 80333, Germany; and.
authors: Roland M
authors: RM
authors: Schmid
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 mh3046@columbia.edu sg2715@columbia.edu.
authors: Matthew S
authors: MS
authors: Hayden
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; mh3046@columbia.edu sg2715@columbia.edu.
authors: Sankar
authors: S
authors: Ghosh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology; D002478:Cells, Cultured; D003872:Dermatitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D020569:Proto-Oncogene Proteins c-rel; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha