Suprabasal spongiosis in acute eczematous dermatitis: cFLIP maintains resistance of basal keratinocytes to T-cell-mediated apoptosis.
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.
Armbruster
Nicole
N
Department of Dermatology, Venereology and Allergology, University of Würzburg, Würzburg, Germany.
Trautmann
Axel
A
Bröcker
Eva-Bettina
EB
Leverkus
Martin
M
Kerstan
Andreas
A
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
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