{"id":15874,"date":"2020-09-18T11:33:29","date_gmt":"2020-09-18T09:33:29","guid":{"rendered":"https:\/\/cri1149.fr\/?post_type=publications&#038;p=15874"},"modified":"2025-09-11T16:48:01","modified_gmt":"2025-09-11T14:48:01","slug":"lc3-associated-phagocytosis-protects-against-inflammation-and-liver-fibrosis-via-immunoreceptor-inhibitory-signaling","status":"publish","type":"publication","link":"https:\/\/cri1149.fr\/en\/publication\/lc3-associated-phagocytosis-protects-against-inflammation-and-liver-fibrosis-via-immunoreceptor-inhibitory-signaling\/","title":{"rendered":"LC3-associated phagocytosis protects against inflammation and liver fibrosis via immunoreceptor inhibitory signaling."},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false,"_EventAllDay":false,"_EventTimezone":"","_EventStartDate":"","_EventEndDate":"","_EventStartDateUTC":"","_EventEndDateUTC":"","_EventShowMap":false,"_EventShowMapLink":false,"_EventURL":"","_EventCost":"","_EventCostDescription":"","_EventCurrencySymbol":"","_EventCurrencyCode":"","_EventCurrencyPosition":"","_EventDateTimeSeparator":"","_EventTimeRangeSeparator":"","_EventOrganizerID":[],"_EventVenueID":[],"_OrganizerEmail":"","_OrganizerPhone":"","_OrganizerWebsite":"","_VenueAddress":"","_VenueCity":"","_VenueCountry":"","_VenueProvince":"","_VenueState":"","_VenueZip":"","_VenuePhone":"","_VenueURL":"","_VenueStateProvince":"","_VenueLat":"","_VenueLng":"","_VenueShowMap":false,"_VenueShowMapLink":false},"category_publication":[],"class_list":["post-15874","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"Sci Transl Med","date_de_publication":"20200415","numero_doi":"","equipe":[144],"auteurs-liste":[{"texte_libre":false,"auteur-lien":13171,"auteur-text":""},{"texte_libre":false,"auteur-lien":13172,"auteur-text":""},{"texte_libre":false,"auteur-lien":13033,"auteur-text":""},{"texte_libre":false,"auteur-lien":13180,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"[:en]Pierre-Marie Choinier[:]"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"[:en] Olivia Picq[:]"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"[:en]Tristan Thibault-Sogorb[:]"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"[:en]Pushpa Hegde[:]"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"[:en]Dorsa Pishvaie[:]"},{"texte_libre":false,"auteur-lien":13031,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"[:en]Linda Broer[:]"},{"texte_libre":false,"auteur-lien":13243,"auteur-text":""},{"texte_libre":false,"auteur-lien":13124,"auteur-text":""},{"texte_libre":false,"auteur-lien":13153,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"[:en]Patrice Codogno[:]"},{"texte_libre":false,"auteur-lien":13121,"auteur-text":""},{"texte_libre":false,"auteur-lien":13108,"auteur-text":""}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/pubmed.ncbi.nlm.nih.gov\/32295902\/"}],"paragraphe":"<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"enc-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">Sustained hepatic and systemic inflammation, particularly originating from monocytes\/macrophages, is a driving force for fibrosis progression to end-stage cirrhosis and underlies the development of multiorgan failure. Reprogramming monocyte\/macrophage phenotype has emerged as a strategy to limit inflammation during chronic liver injury. Here, we report that LC3-associated phagocytosis (LAP), a noncanonical form of autophagy, protects against hepatic and systemic inflammation during chronic liver injury in rodents, with beneficial antifibrogenic effects. LAP is enhanced in blood and liver monocytes from patients with fibrosis and cirrhosis. Pharmacological inhibition of LAP components in human monocytes from patients with cirrhosis or genetic disruption of LAP in mice with chronic liver injury exacerbates both the inflammatory signature in isolated human monocytes and the hepatic inflammatory profile in mice, resulting in enhanced liver fibrosis. Mechanistically, patients with cirrhosis showed increased monocyte expression of Fc fragment of IgG receptor IIA (Fc\u03b3RIIA) and enhanced engulfment of immunoglobulin G in LC3<sup>+<\/sup>\u00a0phagosomes that triggers an Fc\u03b3RIIA\/Src homology region 2 domain-containing phosphatase-1 (SHP-1) inhibitory immunoreceptor tyrosine-based activation motif (ITAMi) anti-inflammatory pathway. Mice overexpressing human Fc\u03b3RIIA in myeloid cells show enhanced LAP in response to chronic liver injury and resistance to inflammation and liver fibrosis. Activation of LAP is lost in monocytes from patients with multiorgan failure and restored by specifically targeting ITAMi signaling with anti-Fc\u03b3RIIA F(ab')<sub>2<\/sub>\u00a0fragments, or with intravenous immunoglobulin (IVIg). These data suggest the existence of an ITAMi-mediated mechanism by which LAP might protect against inflammation. Sustaining LAP may open therapeutic perspectives for patients with chronic liver disease.<\/p>\r\n<\/div>","paragraphe_en":"","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>LC3-associated phagocytosis protects against inflammation and liver fibrosis via immunoreceptor inhibitory signaling. - CRI<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/cri1149.fr\/publication\/lc3-associated-phagocytosis-protects-against-inflammation-and-liver-fibrosis-via-immunoreceptor-inhibitory-signaling\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"LC3-associated phagocytosis protects against inflammation and liver fibrosis via immunoreceptor inhibitory signaling. - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.fr\/publication\/lc3-associated-phagocytosis-protects-against-inflammation-and-liver-fibrosis-via-immunoreceptor-inhibitory-signaling\/\" \/>\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=\"2025-09-11T14:48:01+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.fr\/publication\/lc3-associated-phagocytosis-protects-against-inflammation-and-liver-fibrosis-via-immunoreceptor-inhibitory-signaling\/\",\"url\":\"https:\/\/cri1149.fr\/publication\/lc3-associated-phagocytosis-protects-against-inflammation-and-liver-fibrosis-via-immunoreceptor-inhibitory-signaling\/\",\"name\":\"LC3-associated phagocytosis protects against inflammation and liver fibrosis via immunoreceptor inhibitory signaling. - 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