{"id":22556,"date":"2025-11-20T10:10:41","date_gmt":"2025-11-20T10:10:41","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/poster\/developpement-dune-plateforme-translationnelle-in-vitro-a-in-vivo-il-4-il-13il-4r%ce%b1-dans-un-modele-de-maladie-respiratoire\/"},"modified":"2026-11-12T14:19:56","modified_gmt":"2026-11-12T14:19:56","slug":"developpement-dune-plateforme-translationnelle-in-vitro-a-in-vivo-il-4-il-13il-4r%ce%b1-dans-un-modele-de-maladie-respiratoire","status":"publish","type":"poster","link":"https:\/\/www.sygnaturediscovery.com\/fr\/poster\/developpement-dune-plateforme-translationnelle-in-vitro-a-in-vivo-il-4-il-13il-4r%ce%b1-dans-un-modele-de-maladie-respiratoire\/","title":{"rendered":"D\u00e9veloppement d&rsquo;une plateforme translationnelle in vitro \u00e0 in vivo IL-4\/IL-13:IL-4R\u03b1 dans un mod\u00e8le de maladie respiratoire."},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">L&rsquo;inflammation de type 2 est \u00e0 l&rsquo;origine de nombreuses maladies respiratoires chroniques, notamment l&rsquo;asthme et la BPCO, la signalisation de l&rsquo;IL-4 et de l&rsquo;IL-13 via l&rsquo;IL-4R\u03b1 et la voie JAK\/STAT6 constituant des n\u0153uds centraux de cette voie. Si le succ\u00e8s du dupilumab valide cliniquement l&rsquo;IL-4R\u03b1 comme cible th\u00e9rapeutique, il demeure n\u00e9cessaire de d\u00e9velopper des tests translationnels efficaces pour d\u00e9couvrir et caract\u00e9riser les modulateurs de nouvelle g\u00e9n\u00e9ration de cette voie. En collaboration avec Numerion, Sygnature Discovery a mis au point des plateformes int\u00e9gr\u00e9es <em>in vitro<\/em> et <em>in vivo<\/em> qui relient l&rsquo;interaction et la signalisation de la cible IL-4\/IL-13:IL-4R\u03b1 aux taux de chimiokines en aval dans un mod\u00e8le murin pertinent pour les maladies respiratoires.<\/p>\n\n<p class=\"wp-block-paragraph\">Gr\u00e2ce \u00e0 la r\u00e9sonance plasmonique de surface (RPS), nous avons d\u00e9montr\u00e9 la forte affinit\u00e9 de liaison de l&rsquo;IL-4 et du dupilumab \u00e0 l&rsquo;IL-4R\u03b1 et confirm\u00e9 la perturbation des interactions prot\u00e9ine-prot\u00e9ine IL-4:IL-4R\u03b1 par un test ELISA sandwich. Des essais cellulaires sur des cellules \u00e9pith\u00e9liales pulmonaires BEAS-2B et des spl\u00e9nocytes de souris ont ensuite permis de mettre en \u00e9vidence l&rsquo;activation de la voie de signalisation (pSTAT6) et la lib\u00e9ration de chimiokines en aval (\u00e9otaxine-1), nous permettant ainsi de comparer l&rsquo;anticorps anti-IL-4R\u03b1 dupilumab, valid\u00e9 cliniquement, et l&rsquo;inhibiteur de JAK tofacitinib. Enfin, un mod\u00e8le de souris Balb\/c infect\u00e9e par l&rsquo;IL-13 par voie intranasale a confirm\u00e9 <em>in vivo<\/em> que le tofacitinib r\u00e9duit les concentrations pulmonaires d&rsquo;\u00e9otaxine-1 et d&rsquo;\u00e9otaxine-2 de mani\u00e8re dose-d\u00e9pendante, avec une exposition plasmatique correspondante. Ces r\u00e9sultats compl\u00e8tent une approche translationnelle \u00e0 moyen d\u00e9bit, adapt\u00e9e au profilage de nouvelles th\u00e9rapies ciblant la voie IL-4R\u03b1 dans les maladies respiratoires et autres indications \u00e0 m\u00e9diation Th2.<\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":22558,"template":"","category":[790,817,1262,900,816],"class_list":["post-22556","poster","type-poster","status-publish","has-post-thumbnail","hentry","category-bioscience","category-domaines-therapeutiques","category-essais-biophysiques","category-inflammation-et-immunologie","category-pharmacologie-in-vivo"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v28.8 (Yoast SEO v28.8) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Plateforme IL-4\/IL-13:IL-4R\u03b1 pour les maladies respiratoires | Poster<\/title>\n<meta name=\"description\" content=\"Profilage des modulateurs IL-4R\u03b1 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