Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease

Expression of enzymatically inactive caspase-8, or deletion of caspase-8 from basal epidermal keratinocytes, triggers chronic skin inflammation in mice. Unlike similar inflammation resulting from arrest of nuclear factor κB activation in the epidermal cells, the effect induced by caspase-8 deficiency did not depend on TNF, IL-1, dermal macrophage function, or expression of the toll-like receptor adapter proteins MyD88 or TRIF. Both interferon regulatory factor (IRF) 3 and TANK-binding kinase were constitutively phosphorylated in the caspase-8–deficient epidermis, and knockdown of IRF3 in the epidermis-derived cells from these mice abolished the expression of up-regulated genes. Temporal and spatial analyses of the alterations in gene expression that result from caspase-8 deficiency reveal that the changes are initiated before birth, around the time that cornification develops, and occur mainly in the suprabasal layer. Finally, we found that caspase-8–deficient keratinocytes display an enhanced response to gene activation by transfected DNA. Our findings suggest that an enhanced response to endogenous activators of IRF3 in the epidermis, presumably generated in association with keratinocyte differentiation, contributes to the skin inflammatory process triggered by caspase-8 deficiency

APPROCHE DE LA MALTRAITANCE AUX PERSONNES AGEES EN INSTITUTIONS

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Rôle des voies mitochondriales de l'apoptose au cours de la différenciation terminale des kératinocytes humains

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Bullous pemphigoid in an infant with milk protein allergy

6sinonemixedCinotti, Elisa; Douchet, Catherine; Perrot, Jean Luc; Labeille, Bruno; Allombert-Blaise, Carole; Cambazard, FrédéricCinotti, Elisa; Douchet, Catherine; Perrot, Jean Luc; Labeille, Bruno; Allombert Blaise, Carole; Cambazard, Frédéri

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Cultural influences on the use of effectuation in entrepreneurship The case of German student entrepreneur