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

Autor: De Araujo, Elisabeth, Dessirier, Valérie, Laprée, Geneviève, Valeyrie-Allanore, Laurence, Ortonne, Nicolas, Stathopoulos, Efstathios, Bagot, Martine, Bensussan, Armand, Mockenhaupt, Maja, Roujeau, Jean-Claude, Tsapis, Andreas
Přispěvatelé: Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Maladies auto-immunes et maladies systémiques rares, Hôpital Henri Mondor, Département de pathologie [Mondor], Department of Pathology, University of Crete [Heraklion] (UOC)-School of Medicine, Dokumentationszentrum Schwerer Hautreaktionen (dZh), VU University Medical Center [Amsterdam], this study was funded by grants for the RegiSCAR study (European Commission (QLRT-2002-01738), ORPHANET, GIS-Institut des Maladies Rares in France, DFG (FOR 534) in Germany and a consortium of pharmaceutical companies including Bayer Vital, Boehringer-Ingelheim, GlaxoSmithKline, MSD Sharp & Dohme, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier). The imaging department is supported by grants from the Conseil Regional d'Ile-de-France, the Canceropôle Ile-de-France and the Ministère de la Recherche., Guellaen, Georges
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: Experimental Dermatology
Experimental Dermatology, Wiley, 2011, 20 (2), pp.107-12. ⟨10.1111/j.1600-0625.2010.01176.x⟩
ISSN: 0906-6705
1600-0625
DOI: 10.1111/j.1600-0625.2010.01176.x⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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