{"id":65876,"date":"2023-04-07T17:11:54","date_gmt":"2023-04-07T15:11:54","guid":{"rendered":"https:\/\/cri1149.mlcom-dev.net\/?post_type=publications&#038;p=65876"},"modified":"2025-09-11T16:47:57","modified_gmt":"2025-09-11T14:47:57","slug":"une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait","status":"publish","type":"publication","link":"https:\/\/cri1149.mlcom-dev.net\/en\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/","title":{"rendered":"MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming"},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false},"class_list":["post-65876","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"Nature Commun.","date_de_publication":"20230401","numero_doi":"","equipe":[144],"auteurs-liste":[{"texte_libre":false,"auteur-lien":13180,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Pushpa Hegde"},{"texte_libre":false,"auteur-lien":13254,"auteur-text":""},{"texte_libre":false,"auteur-lien":13171,"auteur-text":""},{"texte_libre":false,"auteur-lien":63550,"auteur-text":""},{"texte_libre":false,"auteur-lien":13217,"auteur-text":"Rola Al Sayegh"},{"texte_libre":false,"auteur-lien":15764,"auteur-text":"Mathilde Cadoux"},{"texte_libre":false,"auteur-lien":13172,"auteur-text":""},{"texte_libre":true,"auteur-lien":"","auteur-text":"Tristan Thibault-Sogorb"},{"texte_libre":true,"auteur-lien":"","auteur-text":"Olivier Lantz"},{"texte_libre":true,"auteur-lien":"","auteur-text":"Mich\u00e8le Goodhardt"},{"texte_libre":false,"auteur-lien":13135,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Pierre de la Grange"},{"texte_libre":false,"auteur-lien":13243,"auteur-text":""},{"texte_libre":false,"auteur-lien":13108,"auteur-text":""}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/pubmed.ncbi.nlm.nih.gov\/37005415\/"}],"paragraphe":"<p><img class=\" wp-image-65880 aligncenter\" src=\"https:\/\/cri1149.mlcom-dev.net\/wp-content\/uploads\/2023\/04\/MAIT-publi-Loterstajn-publi-300x166.jpg\" alt=\"\" width=\"531\" height=\"294\" \/><\/p>\r\n<p style=\"text-align: justify;\">L\u2019\u00e9quipe de Sophie Lotersztajn et H\u00e9l\u00e8ne Gilgenkrantz en collaboration avec celle de V. Paradis (CRI), \u00a0d\u2019O. Lantz (Institut Curie) et de M. Goodhardt (H\u00f4pital St Louis) vient de montrer qu\u2019inhiber l\u2019activation des cellules MAIT (Mucosal Associated Invariant T cells), permet de faire r\u00e9gresser la fibrose h\u00e9patique. L\u2019analyse des m\u00e9canismes impliqu\u00e9s d\u00e9montre que le blocage de l\u2019activation des cellules MAIT interrompt leur dialogue avec les macrophages profibrog\u00e9niques qui jouent un r\u00f4le central dans la fibrose h\u00e9patique et favorise l\u2019\u00e9mergence de macrophages r\u00e9solutifs de la fibrose. Cette \u00e9tude ouvre de nouvelles perspectives th\u00e9rapeutiques pour la prise en charge de la cirrhose pour laquelle aucun traitement n\u2019est actuellement disponible.<\/p>\r\n<blockquote>\r\n<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<\/blockquote>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<blockquote>\r\n<p style=\"text-align: justify;\">Recent data have shown that liver fibrosis can regress even at later stages of cirrhosis and shifting the immune response from pro-inflammatory towards a resolutive profile is considered as a promising option. The immune regulatory networks that govern the shift of the inflammatory phenotype and thus potential reversal of liver fibrosis are lesser known. Here we show that in precision-cut human liver slices obtained from patients with end-stage fibrosis and in mouse models, inhibiting Mucosal-Associated Invariant T (MAIT) cells using pharmacological or antibody-driven approaches, limits fibrosis progression and even regresses fibrosis, following chronic toxic- or non-alcoholic steatohepatitis (NASH)-induced liver injury. Mechanistic studies, combining RNA sequencing, in vivo functional studies (performed in male mice) and co-culture experiments indicate that disruption of the MAIT cell-monocyte\/macrophage interaction results in resolution of fibrosis both by increasing the frequency of restorative Ly6C<sup>lo<\/sup>\u00a0at the expenses of pro-fibrogenic Ly6C<sup>hi<\/sup> monocyte-derived macrophages and promoting an autophagic phenotype in both subsets. Thus, our data show that MAIT cell activation and the consequential phenotype shift of liver macrophages are important pathogenic features of liver fibrosis and could be targeted by anti-fibrogenic therapy.<\/p>\r\n<\/blockquote>\r\n<\/div>\r\n<p style=\"text-align: justify;\">Cette \u00e9tude a fait l\u2019objet d\u2019une publication dans la revue <em>Nature Communications\u00a0<\/em>: 2023 Apr 1;14(1):1830. doi: 10.1038\/s41467-023-37453-5. PMID: 37005415<\/p>","paragraphe_en":"<p><img class=\" wp-image-65880 aligncenter\" src=\"https:\/\/cri1149.mlcom-dev.net\/wp-content\/uploads\/2023\/04\/MAIT-publi-Loterstajn-publi-300x166.jpg\" alt=\"\" width=\"531\" height=\"294\" \/><\/p>\r\n<p style=\"text-align: justify;\">The team of S Loterstajn and H Gilgenkrantz, in collaboration with V Paradis whithin the Centre de Recherche sur l\u2019Inflammation, and the teams of O Lantz (I Curie) and M Goodhardt (Institut St Louis) recently showed that MAIT cell inhibition not only stops liver fibrosis progression but also promotes fibrosis regression. In analyzing the mechanisms involved, the authors showed that blocking MAIT cell activation inhibits the dialog with profibrogenic macrophages and promotes the emergence of resolutive macrophages. These results open new therapeutic perspectives for liver cirrhosis.<\/p>\r\n<blockquote>\r\n<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<\/blockquote>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<blockquote>\r\n<p style=\"text-align: justify;\">Recent data have shown that liver fibrosis can regress even at later stages of cirrhosis and shifting the immune response from pro-inflammatory towards a resolutive profile is considered as a promising option. The immune regulatory networks that govern the shift of the inflammatory phenotype and thus potential reversal of liver fibrosis are lesser known. Here we show that in precision-cut human liver slices obtained from patients with end-stage fibrosis and in mouse models, inhibiting Mucosal-Associated Invariant T (MAIT) cells using pharmacological or antibody-driven approaches, limits fibrosis progression and even regresses fibrosis, following chronic toxic- or non-alcoholic steatohepatitis (NASH)-induced liver injury. Mechanistic studies, combining RNA sequencing, in vivo functional studies (performed in male mice) and co-culture experiments indicate that disruption of the MAIT cell-monocyte\/macrophage interaction results in resolution of fibrosis both by increasing the frequency of restorative Ly6C<sup>lo<\/sup>\u00a0at the expenses of pro-fibrogenic Ly6C<sup>hi<\/sup> monocyte-derived macrophages and promoting an autophagic phenotype in both subsets. Thus, our data show that MAIT cell activation and the consequential phenotype shift of liver macrophages are important pathogenic features of liver fibrosis and could be targeted by anti-fibrogenic therapy.<\/p>\r\n<\/blockquote>\r\n<\/div>\r\n<p style=\"text-align: justify;\">This study is published in Nature Communications\u00a0: 2023 Apr 1;14(1):1830. doi: 10.1038\/s41467-023-37453-5. PMID: 37005415<\/p>","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming - 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=\"MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.mlcom-dev.net\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/\" \/>\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=\"2025-09-11T14:47:57+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\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/\",\"url\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/\",\"name\":\"MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming - CRI\",\"isPartOf\":{\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/#website\"},\"datePublished\":\"2023-04-07T15:11:54+00:00\",\"dateModified\":\"2025-09-11T14:47:57+00:00\",\"breadcrumb\":{\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/cri1149.mlcom-dev.net\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Accueil\",\"item\":\"https:\/\/cri1149.mlcom-dev.net\/en\/cri-home\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Publications\",\"item\":\"https:\/\/cri1149.mlcom-dev.net\/publications\/\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/#website\",\"url\":\"https:\/\/cri1149.mlcom-dev.net\/\",\"name\":\"CRI - Centre de Recherche sur l'Inflammation\",\"description\":\"Centre de Recherche sur l&#039;Inflammation\",\"publisher\":{\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/cri1149.mlcom-dev.net\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"},{\"@type\":\"Organization\",\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/#organization\",\"name\":\"CRI1149\",\"url\":\"https:\/\/cri1149.mlcom-dev.net\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/#\/schema\/logo\/image\/\",\"url\":\"https:\/\/cri1149.mlcom-dev.net\/wp-content\/uploads\/2014\/11\/8.4.2014-logo-CRI.jpg\",\"contentUrl\":\"https:\/\/cri1149.mlcom-dev.net\/wp-content\/uploads\/2014\/11\/8.4.2014-logo-CRI.jpg\",\"width\":215,\"height\":176,\"caption\":\"CRI1149\"},\"image\":{\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/#\/schema\/logo\/image\/\"},\"sameAs\":[\"https:\/\/www.facebook.com\/CRI-Centre-de-recherche-sur-linflammation-100116118884153\",\"https:\/\/www.linkedin.com\/company\/cri-centre-de-recherche-sur-l-inflammation\/\"]}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming - CRI","robots":{"index":"noindex","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"og_locale":"en_US","og_type":"article","og_title":"MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming - CRI","og_url":"https:\/\/cri1149.mlcom-dev.net\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/","og_site_name":"CRI","article_publisher":"https:\/\/www.facebook.com\/CRI-Centre-de-recherche-sur-linflammation-100116118884153","article_modified_time":"2025-09-11T14:47:57+00:00","twitter_card":"summary_large_image","schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/cri1149.mlcom-dev.net\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/","url":"https:\/\/cri1149.mlcom-dev.net\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/","name":"MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming - CRI","isPartOf":{"@id":"https:\/\/cri1149.mlcom-dev.net\/#website"},"datePublished":"2023-04-07T15:11:54+00:00","dateModified":"2025-09-11T14:47:57+00:00","breadcrumb":{"@id":"https:\/\/cri1149.mlcom-dev.net\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/cri1149.mlcom-dev.net\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/cri1149.mlcom-dev.net\/publication\/une-nouvelle-cible-pour-faire-regresser-la-fibrose-hepatique-inhiber-les-lymphocytes-t-associes-aux-muqueuses-mait\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Accueil","item":"https:\/\/cri1149.mlcom-dev.net\/en\/cri-home\/"},{"@type":"ListItem","position":2,"name":"Publications","item":"https:\/\/cri1149.mlcom-dev.net\/publications\/"},{"@type":"ListItem","position":3,"name":"MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming"}]},{"@type":"WebSite","@id":"https:\/\/cri1149.mlcom-dev.net\/#website","url":"https:\/\/cri1149.mlcom-dev.net\/","name":"CRI - Centre de Recherche sur l'Inflammation","description":"Centre de Recherche sur l&#039;Inflammation","publisher":{"@id":"https:\/\/cri1149.mlcom-dev.net\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/cri1149.mlcom-dev.net\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Organization","@id":"https:\/\/cri1149.mlcom-dev.net\/#organization","name":"CRI1149","url":"https:\/\/cri1149.mlcom-dev.net\/","logo":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/cri1149.mlcom-dev.net\/#\/schema\/logo\/image\/","url":"https:\/\/cri1149.mlcom-dev.net\/wp-content\/uploads\/2014\/11\/8.4.2014-logo-CRI.jpg","contentUrl":"https:\/\/cri1149.mlcom-dev.net\/wp-content\/uploads\/2014\/11\/8.4.2014-logo-CRI.jpg","width":215,"height":176,"caption":"CRI1149"},"image":{"@id":"https:\/\/cri1149.mlcom-dev.net\/#\/schema\/logo\/image\/"},"sameAs":["https:\/\/www.facebook.com\/CRI-Centre-de-recherche-sur-linflammation-100116118884153","https:\/\/www.linkedin.com\/company\/cri-centre-de-recherche-sur-l-inflammation\/"]}]}},"post_type":"publication","author_name":"","_links":{"self":[{"href":"https:\/\/cri1149.mlcom-dev.net\/en\/wp-json\/wp\/v2\/publication\/65876","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cri1149.mlcom-dev.net\/en\/wp-json\/wp\/v2\/publication"}],"about":[{"href":"https:\/\/cri1149.mlcom-dev.net\/en\/wp-json\/wp\/v2\/types\/publication"}],"acf:term":[{"embeddable":true,"taxonomy":"equipes","href":"https:\/\/cri1149.mlcom-dev.net\/en\/wp-json\/wp\/v2\/equipes\/144"}],"wp:attachment":[{"href":"https:\/\/cri1149.mlcom-dev.net\/en\/wp-json\/wp\/v2\/media?parent=65876"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}