title: Suprabasal spongiosis in acute eczematous dermatitis: cFLIP maintains resistance of basal keratinocytes to T-cell-mediated apoptosis.
abstract: In acute eczematous dermatitis, keratinocyte (KC) apoptosis caused by dermis-infiltrating, activated T cells plays a crucial pathogenetic role in the development of spongiosis, the histopathological hallmark of acute eczema. Remarkably, T-cell-mediated apoptosis of single KC, as well as spongiosis, is located predominantly in suprabasal epidermal layers, suggesting that antiapoptotic mechanisms protect basal KC. The cellular Flice-inhibitory protein (cFLIP) is known to block apoptotic CD95-signaling, and may therefore account for such a protection of basal KC. HaCaT KCs retrovirally transduced with the long form of cFLIP were effectively protected against T-cell-mediated apoptosis in KC monolayer/CD4(+) T-cell cocultures. In situ correlation of cFLIP protein expression and KC apoptosis in lesional eczematous skin showed a highly restricted expression of cFLIP in basal KC, whereas cleaved caspase-3 (as a surrogate marker of apoptosis) was detected predominantly in suprabasal epidermal layers. Thus, the modulation of the CD95 signaling pathway by the cell-intrinsic caspase-8 inhibitor cFLIP in basal KC may explain the spatial localization of spongiosis in suprabasal epidermal layers, and provides new insights into the pathogenesis of spongiosis formation in eczematous dermatitis.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University of Würzburg, Würzburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Armbruster
authors.forename: Axel
authors.initials: A
authors.lastname: Trautmann
authors.forename: Eva-Bettina
authors.initials: EB
authors.lastname: Bröcker
authors.forename: Martin
authors.initials: M
authors.lastname: Leverkus
authors.forename: Andreas
authors.initials: A
authors.lastname: Kerstan
mesh_terms: D000208:Acute Disease; D017209:Apoptosis / Q000276:immunology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004485:Eczema / Q000276:immunology* / Q000473:pathology*; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology*; D008010:Lichen Planus / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014162:Transfection
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D049452:Green Fluorescent Proteins; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8