Death ligand TRAIL, secreted by CD1a and CD14 cells in blister fluids, is involved in killing keratinocytes in toxic epidermal necrolysis.: TRAIL in toxic epidermal necrolysisReportar como inadecuado




Death ligand TRAIL, secreted by CD1a and CD14 cells in blister fluids, is involved in killing keratinocytes in toxic epidermal necrolysis.: TRAIL in toxic epidermal necrolysis - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

* Corresponding author 1 DIO U976 - Immunologie, dermatologie, oncologie ; Oncodermatologie, immunologie et cellules souches cutanées 2 IMRB - Institut Mondor de recherche biomédicale 3 Service de dermatologie Mondor 4 Maladies auto-immunes et maladies systémiques rares 5 Département de pathologie Mondor 6 Department of Pathology 7 dZh - Dokumentationszentrum Schwerer Hautreaktionen

Abstract : Toxic epidermal necrolysis TEN is characterized by an acute detachment and destruction of keratinocytes, affecting large areas of the skin. It is often related to adverse drug reactions. Previous studies have shown that effector CD8+ T cells, which accumulate in the blister fluid, are functionally cytotoxic and act through a classical perforin-granzyme B pathway. It has recently been shown that these cytotoxic T cells also secrete granulysin peptide, which is lethal to keratinocytes. These cytotoxic T cells exert their killer activity against autologous keratinocytes in the presence of the drug. However, they are unlikely to be the only effectors of TEN. We therefore searched for soluble death factors in the blister fluids that might kill keratinocytes. We found that the amounts of interferon-γ, TRAIL and TNF-α proteins were significantly greater in TEN blister fluids than in all controls normal sera, TEN sera, burns and Eosinophilic pustular folliculitis blister fluids and TNF-like weak inducer of apoptosis TWEAK amounts are also greater in all controls except burns. We showed that these proteins acted in synergy to induce the death of keratinocytes in vitro. We also found that TRAIL and TWEAK were secreted by CD1a+ and CD14+ cells present in the blister fluids. Thus, in addition to MHC class I-restricted cytotoxic T lymphocytes CTLs, which lyse keratinocytes, ligands secreted by non-lymphoid cells capable of inducing keratinocyte death in an MHC class I-independent manner, also seem to be present in the blister fluids of patients with TEN.

Keywords : human apoptosis cytotoxicity skin TNFSF superfamily





Autor: Elisabeth De Araujo - Valérie Dessirier - Geneviève Laprée - Laurence Valeyrie-Allanore - Nicolas Ortonne - Efstathios Stathop

Fuente: https://hal.archives-ouvertes.fr/



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