{"id":74395,"date":"2025-05-15T15:24:51","date_gmt":"2025-05-15T13:24:51","guid":{"rendered":"https:\/\/cri1149.mlcom-dev.net\/?post_type=publications&#038;p=74395"},"modified":"2025-12-05T17:19:38","modified_gmt":"2025-12-05T16:19:38","slug":"defective-autophagy-in-cd4-t-cells-drives-liver-fibrosis-via-type-3-inflammation","status":"publish","type":"publication","link":"https:\/\/cri1149.mlcom-dev.net\/en\/publication\/defective-autophagy-in-cd4-t-cells-drives-liver-fibrosis-via-type-3-inflammation\/","title":{"rendered":"Defective autophagy in CD4 T cells drives liver fibrosis via type 3 inflammation"},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false},"class_list":["post-74395","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"Nature Communications","date_de_publication":"20250424","numero_doi":"10.1038\/s41467-025-59218-y","equipe":[144],"auteurs-liste":[{"texte_libre":false,"auteur-lien":13217,"auteur-text":""},{"texte_libre":false,"auteur-lien":13171,"auteur-text":""},{"texte_libre":false,"auteur-lien":63550,"auteur-text":""},{"texte_libre":false,"auteur-lien":71596,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Maxime Gasperment"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Sukriti Baweja"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Marc-Anthony Chouillard"},{"texte_libre":false,"auteur-lien":65334,"auteur-text":""},{"texte_libre":false,"auteur-lien":15764,"auteur-text":""},{"texte_libre":false,"auteur-lien":13180,"auteur-text":""},{"texte_libre":false,"auteur-lien":63554,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Tristan Thibault-Sogorb"},{"texte_libre":false,"auteur-lien":13254,"auteur-text":""},{"texte_libre":false,"auteur-lien":13135,"auteur-text":""},{"texte_libre":false,"auteur-lien":13153,"auteur-text":""},{"texte_libre":false,"auteur-lien":47152,"auteur-text":""},{"texte_libre":false,"auteur-lien":13243,"auteur-text":""},{"texte_libre":false,"auteur-lien":13172,"auteur-text":""},{"texte_libre":false,"auteur-lien":13108,"auteur-text":""}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/www.nature.com\/articles\/s41467-025-59218-y"}],"paragraphe":"","paragraphe_en":"<h2 id=\"Abs1\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"Abs1-content\" class=\"c-article-section__content\">\r\n<p style=\"text-align: justify;\">Conventional CD4 T cells represent a major source of inflammatory mediators that drive progression of chronic liver disease to fibrosis and to end-stage cirrhosis. Identification of T cell pathways that limits the inflammatory response could thus have therapeutic relevance. Here we show, using both human samples and mouse models, that autophagy is deficient in CD4 T cells from patients with advanced fibrosis, and that loss of autophagy following genomic deletion of ATG5 in T cells is associated with the emergence of pathogenic IL-17A\u2009+\u2009IFN-\u03b3\u2009+\u2009Th17 T cells that drive liver fibrosis in mice. Mechanistically, liver CD4 T cells lacking autophagy display a Th17 glycolytic phenotype associated with enhanced type 3 cytokine (i.e., IL-17A and GM-CSF) release, shifting hepatic myofibroblasts, hepatocytes and macrophages toward a proinflammatory phenotype. We also show that autophagy can be rescued in CD4 T cells from patients with extensive liver fibrosis, leading to decreased frequency of pathogenic Th17 cells and reduced GM-CSF levels; in addition, limited fibrosis is observed in mice in which Rubicon, a negative regulator of autophagy, is deleted specifically in their T cells. Our findings thus implicate autophagy in CD4 T cells as a key therapeutic target to control inflammation-driven fibrosis during chronic liver injury.<\/p>\r\n<p><img class=\" wp-image-74396 aligncenter\" src=\"https:\/\/cri1149.mlcom-dev.net\/wp-content\/uploads\/2025\/05\/Graphical-abstract-rola-300x240.png\" alt=\"\" width=\"711\" height=\"568\" \/><\/p>\r\n<\/div>","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Defective autophagy in CD4 T cells drives liver fibrosis via type 3 inflammation - 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=\"Defective autophagy in CD4 T cells drives liver fibrosis via type 3 inflammation - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.mlcom-dev.net\/publication\/defective-autophagy-in-cd4-t-cells-drives-liver-fibrosis-via-type-3-inflammation\/\" \/>\n<meta property=\"og:site_name\" content=\"CRI\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/CRI-Centre-de-recherche-sur-linflammation-100116118884153\" \/>\n<meta property=\"article:modified_time\" content=\"2025-12-05T16:19:38+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/defective-autophagy-in-cd4-t-cells-drives-liver-fibrosis-via-type-3-inflammation\/\",\"url\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/defective-autophagy-in-cd4-t-cells-drives-liver-fibrosis-via-type-3-inflammation\/\",\"name\":\"Defective autophagy in CD4 T cells drives liver fibrosis via type 3 inflammation - 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