title: Crosstalk between keratinocytes and adaptive immune cells in an IkappaBalpha protein-mediated inflammatory disease of the skin.
abstract: 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 IkappaBalpha protein (Ikba(Delta)(/Delta)) as well as concomitant deletion of Ikba specifically in keratinocytes and T cells (Ikba(K5Delta/K5Delta lckDelta/lckDelta)) 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 Ikba in keratinocytes or lymphocytes showed inflammation limited to the dermal compartment or a normal skin phenotype, respectively. Targeted deletion of RelA from epidermal keratinocytes completely rescued the inflammatory skin phenotype of Ikba(Delta)(/Delta) mice. This finding emphasizes the important role of aberrant NF-kappaB activation in both keratinocytes and lymphocytes in the development of the observed inflammatory skin changes.
authors: Department of Dermatology and Allergology, Ludwig-Maximilians-University Munich, Frauenlobstrasse 9-11, D-80337 Munich, Germany.
authors: Bernd
authors: B
authors: Rebholz
authors: Ingo
authors: I
authors: Haase
authors: Birgit
authors: B
authors: Eckelt
authors: Stephan
authors: S
authors: Paxian
authors: Michael J
authors: MJ
authors: Flaig
authors: Kamran
authors: K
authors: Ghoreschi
authors: Sergei A
authors: SA
authors: Nedospasov
authors: Reinhard
authors: R
authors: Mailhammer
authors: Svenja
authors: S
authors: Debey-Pascher
authors: Joachim L
authors: JL
authors: Schultze
authors: Günther
authors: G
authors: Weindl
authors: Irmgard
authors: I
authors: Förster
authors: Ralf
authors: R
authors: Huss
authors: Athanasios
authors: A
authors: Stratis
authors: Thomas
authors: T
authors: Ruzicka
authors: Martin
authors: M
authors: Röcken
authors: Klaus
authors: K
authors: Pfeffer
authors: Roland M
authors: RM
authors: Schmid
authors: Rudolf A
authors: RA
authors: Rupec
mesh_terms: D000038:Abscess / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000818:Animals; D002450:Cell Communication; D003872:Dermatitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D017353:Gene Deletion; D020672:I-kappa B Proteins / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000276:immunology* / Q000473:pathology; D007633:Keratins / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D000072000:NF-KappaB Inhibitor alpha; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D008233:Lymphotoxin-alpha; C000606205:Nfkbia protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D007633:Keratins