{"id":13415,"date":"2014-07-25T09:39:47","date_gmt":"2014-07-25T08:39:47","guid":{"rendered":"http:\/\/cyber.pixilie.fr\/?post_type=publications&#038;p=13415"},"modified":"2025-09-11T16:48:05","modified_gmt":"2025-09-11T14:48:05","slug":"shifting-fc%ce%b3riia-itam-from-activation-to-inhibitory-configuration-ameliorates-arthritis","status":"publish","type":"publication","link":"https:\/\/cri1149.mlcom-dev.net\/en\/publication\/shifting-fc%ce%b3riia-itam-from-activation-to-inhibitory-configuration-ameliorates-arthritis\/","title":{"rendered":"Shifting Fc\u03b3RIIA-ITAM from activation to inhibitory configuration ameliorates arthritis"},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false},"class_list":["post-13415","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"J Clin Invest.","date_de_publication":"20140725","numero_doi":"","equipe":[138],"auteurs-liste":[{"texte_libre":false,"auteur-lien":13033,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Hayem G"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"J\u00f6nsson F"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Rossato E"},{"texte_libre":false,"auteur-lien":13038,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Boussetta T"},{"texte_libre":false,"auteur-lien":13071,"auteur-text":""},{"texte_libre":false,"auteur-lien":13098,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Goujon JM"},{"texte_libre":false,"auteur-lien":13030,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Bruhns P"},{"texte_libre":false,"auteur-lien":13121,"auteur-text":""}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25061875"}],"paragraphe":"<h3 style=\"text-align: justify;\">Abstract<\/h3>\r\n<div class=\"\">\r\n<p style=\"text-align: justify;\">Rheumatoid arthritis-associated (RA-associated) inflammation is mediated through the interaction between RA IgG immune complexes and IgG Fc receptors on immune cells. Polymorphisms within the gene encoding the human IgG Fc receptor IIA (hFc\u03b3RIIA) are associated with an increased risk of developing RA. Within the hFc\u03b3RIIA intracytoplasmic domain, there are 2 conserved tyrosine residues arranged in a noncanonical immunoreceptor tyrosine-based activation motif (ITAM). Here, we reveal that inhibitory engagement of the hFc\u03b3RIIA ITAM either with anti-hFc\u03b3RII F(ab')2 fragments or intravenous hIgG (IVIg) ameliorates RA-associated inflammation, and this effect was characteristic of previously described inhibitory ITAM (ITAMi) signaling for hFc\u03b1RI and hFc\u03b3RIIIA, but only involves a single tyrosine. In hFc\u03b3RIIA-expressing mice, arthritis induction was inhibited following hFc\u03b3RIIA engagement. Moreover, hFc\u03b3RIIA ITAMi-signaling reduced ROS and inflammatory cytokine production through inhibition of guanine nucleotide exchange factor VAV-1 and IL-1 receptor-associated kinase 1 (IRAK-1), respectively. ITAMi signaling was mediated by tyrosine 304 (Y304) within the hFc\u03b3RIIA ITAM, which was required for recruitment of tyrosine kinase SYK and tyrosine phosphatase SHP-1. Anti-hFc\u03b3RII F(ab')2 treatment of inflammatory synovial cells from RA patients inhibited ROS production through induction of ITAMi signaling. These data suggest that shifting constitutive hFc\u03b3RIIA-mediated activation to ITAMi signaling could ameliorate RA-associated inflammation.<\/p>\r\n<\/div>","paragraphe_en":"","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Shifting Fc\u03b3RIIA-ITAM from activation to inhibitory configuration ameliorates arthritis - 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=\"Shifting Fc\u03b3RIIA-ITAM from activation to inhibitory configuration ameliorates arthritis - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.mlcom-dev.net\/publication\/shifting-fc\u03b3riia-itam-from-activation-to-inhibitory-configuration-ameliorates-arthritis\/\" \/>\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=\"2025-09-11T14:48:05+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\/shifting-fc%ce%b3riia-itam-from-activation-to-inhibitory-configuration-ameliorates-arthritis\/\",\"url\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/shifting-fc%ce%b3riia-itam-from-activation-to-inhibitory-configuration-ameliorates-arthritis\/\",\"name\":\"Shifting Fc\u03b3RIIA-ITAM from activation to inhibitory configuration ameliorates arthritis - 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