title: The caspase-cleaved form of LYN mediates a psoriasis-like inflammatory syndrome in mice.
abstract: We showed previously that Lyn is a substrate for caspases, a family of cysteine proteases, involved in the regulation of apoptosis and inflammation. Here, we report that expression of the caspase-cleaved form of Lyn (LynDeltaN), in mice, mediates a chronic inflammatory syndrome resembling human psoriasis. Genetic ablation of TNF receptor 1 in a LynDeltaN background rescues a normal phenotype, indicating that LynDeltaN mice phenotype is TNF-alpha-dependent. The predominant role of T cells in the disease occurring in LynDeltaN mice was highlighted by the distinct improvement of LynDeltaN mice phenotype in a Rag1-deficient background. Using pan-genomic profiling, we also established that LynDeltaN mice show an increased expression of STAT-3 and inhibitory members of the NFkappaB pathway. Accordingly, LynDeltaN alters NFkappaB activity underlying a link between inhibition of NFkappaB and LynDeltaN mice phenotype. Finally, analysis of Lyn expression in human skin biopsies of psoriatic patients led to the detection of Lyn cleavage product whose expression correlates with the activation of caspase 1. Our data identify a new role for Lyn as a regulator of psoriasis through its cleavage by caspases.
authors: INSERM, U895, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 2, Nice, France.
authors: Sandrine
authors: S
authors: Marchetti
authors: Parvati
authors: P
authors: Gamas
authors: Nathalie
authors: N
authors: Belhacène
authors: Sebastien
authors: S
authors: Grosso
authors: Ludivine A
authors: LA
authors: Pradelli
authors: Pascal
authors: P
authors: Colosetti
authors: Claus
authors: C
authors: Johansen
authors: Lars
authors: L
authors: Iversen
authors: Marcel
authors: M
authors: Deckert
authors: Fréderic
authors: F
authors: Luciano
authors: Paul
authors: P
authors: Hofman
authors: Nicolas
authors: N
authors: Ortonne
authors: Abdallah
authors: A
authors: Khemis
authors: Bernard
authors: B
authors: Mari
authors: Jean-Paul
authors: JP
authors: Ortonne
authors: Jean-Ehrland
authors: JE
authors: Ricci
authors: Patrick
authors: P
authors: Auberger
mesh_terms: D000818:Animals; D001706:Biopsy; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000033:anatomy & histology / Q000473:pathology*; D013950:Thymus Gland / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D020169:Caspases