{"id":65320,"date":"2023-03-09T12:26:36","date_gmt":"2023-03-09T11:26:36","guid":{"rendered":"https:\/\/cri1149.fr\/?post_type=publications&#038;p=65320"},"modified":"2025-09-11T16:47:58","modified_gmt":"2025-09-11T14:47:58","slug":"insulin-regulated-aminopeptidase-contributes-to-setting-the-intensity-of-fcr-mediated-inflammation","status":"publish","type":"publication","link":"https:\/\/cri1149.fr\/en\/publication\/insulin-regulated-aminopeptidase-contributes-to-setting-the-intensity-of-fcr-mediated-inflammation\/","title":{"rendered":"Insulin-regulated aminopeptidase contributes to setting the intensity of FcR-mediated inflammation"},"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-65320","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"Front Immunol.","date_de_publication":"20221027","numero_doi":"","equipe":[101],"auteurs-liste":[{"texte_libre":false,"auteur-lien":13190,"auteur-text":""},{"texte_libre":false,"auteur-lien":13185,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Cyril Long\u00e9"},{"texte_libre":false,"auteur-lien":16349,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Ga\u00ebl M\u00e9nasch\u00e9"},{"texte_libre":false,"auteur-lien":13030,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Nadine Varin-Blank"},{"texte_libre":false,"auteur-lien":13037,"auteur-text":""},{"texte_libre":false,"auteur-lien":13153,"auteur-text":""},{"texte_libre":false,"auteur-lien":13033,"auteur-text":""}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/pubmed.ncbi.nlm.nih.gov\/36389775\/"}],"paragraphe":"<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">The function of intracellular trafficking in immune-complex triggered inflammation remains poorly understood. Here, we investigated the role of Insulin-Regulated Amino Peptidase (IRAP)-positive endosomal compartments in Fc receptor (FcR)-induced inflammation. Less severe Fc\u03b3R-triggered arthritis, active systemic anaphylaxis and Fc\u03b5RI-triggered passive systemic anaphylaxis were observed in IRAP-deficient\u00a0<i>versus<\/i>\u00a0wild-type mice. In mast cells Fc\u03b5RI stimulation induced rapid plasma membrane recruitment of IRAP-positive endosomes. IRAP-deficient cells exhibited reduced secretory responses, calcium signaling and activating Syk<sup>Y519\/520<\/sup>\u00a0phosphorylation albeit receptor tyrosine phosphorylation on \u03b2 and \u03b3 subunits was not different. By contrast, in the absence of IRAP, SHP1-inactivating phosphorylation on Ser<sup>591<\/sup>\u00a0that controls Syk activity was decreased.\u00a0<i>Ex-vivo<\/i>\u00a0cell profiling after Fc\u03b3R-triggered anaphylaxis confirmed decreased phosphorylation of both Syk<sup>Y519\/520<\/sup>\u00a0and SHP-1<sup>S591<\/sup>\u00a0in IRAP-deficient neutrophils and monocytes. Thus, IRAP-positive endosomal compartments, in promoting inhibition of SHP-1 during FcR signaling, control the extent of phosphorylation events at the plasma membrane and contribute to setting the intensity of immune-complex triggered inflammatory diseases.<\/p>\r\n<\/div>","paragraphe_en":"<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">The function of intracellular trafficking in immune-complex triggered inflammation remains poorly understood. Here, we investigated the role of Insulin-Regulated Amino Peptidase (IRAP)-positive endosomal compartments in Fc receptor (FcR)-induced inflammation. Less severe Fc\u03b3R-triggered arthritis, active systemic anaphylaxis and Fc\u03b5RI-triggered passive systemic anaphylaxis were observed in IRAP-deficient\u00a0<i>versus<\/i>\u00a0wild-type mice. In mast cells Fc\u03b5RI stimulation induced rapid plasma membrane recruitment of IRAP-positive endosomes. IRAP-deficient cells exhibited reduced secretory responses, calcium signaling and activating Syk<sup>Y519\/520<\/sup>\u00a0phosphorylation albeit receptor tyrosine phosphorylation on \u03b2 and \u03b3 subunits was not different. By contrast, in the absence of IRAP, SHP1-inactivating phosphorylation on Ser<sup>591<\/sup>\u00a0that controls Syk activity was decreased.\u00a0<i>Ex-vivo<\/i>\u00a0cell profiling after Fc\u03b3R-triggered anaphylaxis confirmed decreased phosphorylation of both Syk<sup>Y519\/520<\/sup>\u00a0and SHP-1<sup>S591<\/sup>\u00a0in IRAP-deficient neutrophils and monocytes. Thus, IRAP-positive endosomal compartments, in promoting inhibition of SHP-1 during FcR signaling, control the extent of phosphorylation events at the plasma membrane and contribute to setting the intensity of immune-complex triggered inflammatory diseases.<\/p>\r\n<\/div>","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Insulin-regulated aminopeptidase contributes to setting the intensity of FcR-mediated inflammation - 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\/insulin-regulated-aminopeptidase-contributes-to-setting-the-intensity-of-fcr-mediated-inflammation\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Insulin-regulated aminopeptidase contributes to setting the intensity of FcR-mediated inflammation - 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