GSE99379 cFLIP prevents TNFR1-dependent lethal dermatitis and TNFR1-independent blockade of epidermal differentiation

Contributors : Xuehua Piao ; Ryosuke Miura ; Ryodai Shindo ; Hiroyasu NakanoSeries Type : Expression profiling by arrayOrganism : Mus musculusCellular FLICE-inhibitory protein (cFLIP) prevents the development of dermatitis by blocking TNF α-dependent apoptosis of keratinocytes. However, it is unclear whether TNFα-independent signal might also contribute to the development of dermatitis in epidermis-specific Cflar-deficient (Cflar) mice. Here we show that Cflar;Tnfrsf1a-/- mice were born at the expected Mende lian ratio, but developed severe dermatitis and succumbed soon after birth. While keratinocytes still died by apoptosis, expression of epidermal differentiation markers, such as Loricrin, Filaggrin, and Keratin (Krt)10, but not Krt5 were severely downregulated in the skin of Cflar;Tnfrsf 1a-/- mice at both mRNA and protein levels. Conversely, inflammatory cytokines, such as interleukin (IL)-6 and Il17a were elevated in the skin of Cflar ;Tnfrsf1a-/- mice. Treatment of primary keratinocytes with IL-6, to a lesser extent IL-17A suppressed expression of Loricrin, Filaggrin, and Krt10. Together, cFLIP suppresses TNFR1-independent apoptosis of keratinocytes and prevents IL-6-dependent blockade of epidermal differentiation.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research