{"id":4900,"date":"2015-03-04T16:08:55","date_gmt":"2015-03-04T15:08:55","guid":{"rendered":"http:\/\/www.cri1149.fr\/?page_id=4900"},"modified":"2025-12-03T18:00:50","modified_gmt":"2025-12-03T17:00:50","slug":"resume-ziad-elnhabani","status":"publish","type":"page","link":"https:\/\/cri1149-dev.mlcom-dev.net\/en\/resume-ziad-elnhabani\/","title":{"rendered":"R\u00e9sum\u00e9 Ziad ELNHABANI"},"content":{"rendered":"<p style=\"text-align: justify;\"><a href=\"https:\/\/cri1149-dev.mlcom-dev.net\/wp-content\/uploads\/2015\/02\/logo2_upmc.gif\">\u00a0<\/a><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #808080; font-family: arial,helvetica,sans-serif; font-size: 10pt;\"><strong>R<\/strong><strong>\u00c9SUM\u00c9<\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #808080; font-family: arial,helvetica,sans-serif; font-size: 10pt;\">La maladie de Crohn (MC) est une maladie inflammatoire chronique de l\u2019intestin. Sa physiopathologie est caract\u00e9ris\u00e9e par une r\u00e9action immunitaire excessive en r\u00e9ponse \u00e0 des anomalies du microbiote chez des individus g\u00e9n\u00e9tiquement pr\u00e9dispos\u00e9s. Bien que les mutations du g\u00e8ne <em>NOD2<\/em> aient \u00e9t\u00e9 associ\u00e9es \u00e0 la MC, leur r\u00f4le dans la gen\u00e8se de la maladie reste inconnu. Nod2 est un r\u00e9cepteur intracellulaire au muramyl dipeptide, un fragment du peptidoglycane des bact\u00e9ries Gram positif et Gram n\u00e9gatif. De r\u00e9centes \u00e9tudes ont montr\u00e9 que <em>Nod2<\/em> jouait un r\u00f4le dans le contr\u00f4le du microbiote et l\u2019hom\u00e9ostasie de la muqueuse intestinale. Les objectifs de cette th\u00e8se \u00e9taient d\u2019\u00e9tudier l\u2019impact de l\u2019invalidation de <em>Nod2<\/em> dans les cellules \u00e9pith\u00e9liales et immunitaires sur le microbiote et la fonction de la muqueuse digestive en utilisant des mod\u00e8les animaux et cellulaires. Nous avons montr\u00e9 que les souris d\u00e9ficientes pour le g\u00e8ne <em>Nod2<\/em> pr\u00e9sentaient des alt\u00e9rations de la composition du microbiote il\u00e9ale et colique et que ces alt\u00e9rations \u00e9taient ind\u00e9pendantes des facteurs environnementaux. Cependant, la dysbiose bact\u00e9rienne li\u00e9e \u00e0 l\u2019invalidation de <em>Nod2<\/em> n\u2019\u00e9tait pas capable d\u2019affecter la fonctionnalit\u00e9 de l\u2019\u00e9pith\u00e9lium intestinal. De plus, nous avons mis en \u00e9vidence que l\u2019expression de <em>Nod2<\/em> dans le compartiment \u00e9pith\u00e9lial contr\u00f4lait la stabilit\u00e9 du microbiote en modulant l\u2019expression des mucines et des peptides antimicrobiens. \u00c0 l\u2019inverse, <em>Nod2<\/em> dans le compartiment immunitaire r\u00e9gulait les fonctions de l\u2019\u00e9pith\u00e9lium et participait \u00e0 l\u2019acquisition de ce dernier durant les six premi\u00e8res semaines de vie. Parmi les cellules immunitaires, nous avons \u00e9galement observ\u00e9 que l\u2019invalidation de <em>Nod2<\/em> dans les lymphocytes T-CD4<em><sup>+<\/sup><\/em> \u00e9tait n\u00e9cessaire et suffisante pour alt\u00e9rer la perm\u00e9abilit\u00e9 de l\u2019\u00e9pith\u00e9lium intestinal. Cependant, l\u2019activation de Nod2 par son ligand dans les cellules \u00e9pith\u00e9liales \u00e9tait capable de normaliser l\u2019augmentation de la perm\u00e9abilit\u00e9 induite par les lymphocytes T-CD4<sup>+<\/sup>, en bloquant l\u2019expression et l\u2019activit\u00e9 de la MLCK (pour <em>Myosin light chain kinase<\/em>). Enfin, nous avons montr\u00e9 que Nod2 prot\u00e9geait l\u2019intestin gr\u00eale en cas d\u2019inflammation colique. L\u2019ensemble de ces r\u00e9sultats apporte de nouveaux \u00e9l\u00e9ments dans la connaissance des m\u00e9canismes par lesquels les mutations du g\u00e8ne <em>Nod2<\/em> participent au d\u00e9veloppement de la MC.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #808080; font-family: arial,helvetica,sans-serif; font-size: 10pt;\"><strong>A<\/strong><strong>bstract<\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #808080; font-family: arial,helvetica,sans-serif; font-size: 10pt;\">Crohn disease (CD) is a chronic inflammatory bowel disease characterized by an excessive immune reaction in response to abnormal microbiota in genetically predisposed individuals. Although <em>NOD2<\/em> mutations have been associated with susceptibility to CD, their role in the genesis of the human disease remains unclear. Nod2 is a sensor of muramyl dipeptide that is the minimal bioactive peptidoglycan fragment from both Gram positive and Gram negative bacteria. Numerous studies have shown that <em>Nod2<\/em> deficiency alters microbiota composition and the homeostasis of the intestinal mucosa. The aims of this thesis were to study the role of Nod2 inside immune and epithelial compartment in the control of the gut microbiota and mucosal homeostasis using animal and cellular models. We have shown <em>Nod2<\/em> Knockout mice exhibited a microbiota dysbiosis at both ileal and colonic location and that these alterations of intestinal microbiota were independent of environmental factors. <em>Nod2<\/em> inside hematopoietic lineage regulated the barrier function and participated in the control of bacterial acquisition for the early stage \u00a0(Nod2 deficiency inside epithelial compartment maintained the bacterial dysbiosis by regulating the secretion of both mucins and antimicrobial peptides. Among immune cells, we have also shown that <em>Nod2<\/em> deficiency in CD4<sup>+<\/sup> T cells was sufficient to modify the intestinal barrier function. Nevertheless, activation of <em>Nod2<\/em> by their ligands normalized the increase of permeability induced by CD4<sup>+<\/sup> T cells by MLCK-dependent mechanisms. Finally, we demonstrated that Nod2 protected the small intestine against colitis. Taken together, these results provide new evidence in favor of the mechanism by which NOD2 mutations are involved in the pathogenesis of CD.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #808080; font-family: arial,helvetica,sans-serif; font-size: 10pt;\">\u00a0<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #808080; font-family: arial,helvetica,sans-serif; font-size: 10pt;\">\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>\u00a0 R\u00c9SUM\u00c9 La maladie de Crohn (MC) est une maladie inflammatoire chronique de l\u2019intestin. Sa physiopathologie est caract\u00e9ris\u00e9e par une r\u00e9action immunitaire excessive en r\u00e9ponse \u00e0 des anomalies du microbiote chez des individus g\u00e9n\u00e9tiquement pr\u00e9dispos\u00e9s. Bien que les mutations du g\u00e8ne NOD2 aient \u00e9t\u00e9 associ\u00e9es \u00e0 la MC, leur r\u00f4le dans la gen\u00e8se de la [&hellip;]<\/p>\n","protected":false},"author":9,"featured_media":0,"parent":0,"menu_order":500,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-4900","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>R\u00e9sum\u00e9 Ziad ELNHABANI - CRI<\/title>\n<meta name=\"robots\" content=\"noindex, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"R\u00e9sum\u00e9 Ziad ELNHABANI - CRI\" \/>\n<meta property=\"og:description\" content=\"\u00a0 R\u00c9SUM\u00c9 La maladie de Crohn (MC) est une maladie inflammatoire chronique de l\u2019intestin. 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