{"id":80396,"date":"2025-02-20T11:18:59","date_gmt":"2025-02-20T11:18:59","guid":{"rendered":"https:\/\/cri1149.fr\/publication\/lair-1-acts-as-an-immune-checkpoint-on-activated-ilc2s-and-regulates-the-induction-of-airway-hyperreactivity\/"},"modified":"2025-02-20T11:18:59","modified_gmt":"2025-02-20T11:18:59","slug":"lair-1-acts-as-an-immune-checkpoint-on-activated-ilc2s-and-regulates-the-induction-of-airway-hyperreactivity","status":"publish","type":"publication","link":"https:\/\/cri1149.fr\/en\/publication\/lair-1-acts-as-an-immune-checkpoint-on-activated-ilc2s-and-regulates-the-induction-of-airway-hyperreactivity\/","title":{"rendered":"LAIR-1 acts as an immune checkpoint on activated ILC2s and regulates the induction of airway hyperreactivity"},"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-80396","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"J Allergy Clin Immunol.","date_de_publication":"20230101","numero_doi":"10.1016\/j.jaci.2021.05.042","equipe":[383],"auteurs-liste":[{"texte_libre":false,"auteur-lien":73990,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Pedram Shafiei-Jahani"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Benjamin P Hurrell"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Jacob D Painter"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Christine Quach"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Emily Howard"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Omid Akbari "}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC8674385\/"}],"paragraphe":"

Abstract<\/h2>\n
\n

Background:<\/h3>\n

Type-2 innate lymphoid cells (ILC2s) are relevant players in type-2 asthma. They initiate eosinophil infiltration and airway hyperreactivity (AHR) through cytokine secretion. Leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) is an inhibitory receptor considered as an immune checkpoint in different inflammatory diseases. <\/p>\n<\/section>\n

\n

Objective:<\/h3>\n

Here we investigated the expression of LAIR-1 and assessed its role in human and murine ILC2s.<\/p>\n<\/section>\n

\n

Methods:<\/h3>\n

WT and LAIR-1 KO mice were intranasally challenged with IL-33 and pulmonary ILC2s were sorted to perform an ex-vivo<\/em> comparative study, based on RNA sequencing and flow cytometry. We next studied the impact of LAIR-1 deficiency on AHR and lung inflammation using knock-out mice and adoptive transfer experiments in Rag2<\/em>\u2212\/\u2212<\/sup> Il2rg<\/em>\u2212\/\u2212<\/sup> mice. Knockdown antisense strategies and humanized mice were used to assess the role of LAIR-1 in human ILC2s. <\/p>\n<\/section>\n

\n

Results:<\/h3>\n

We have demonstrated that LAIR-1 is inducible on activated ILC2s and downregulates cytokine secretion and effector function. LAIR-1 signaling in ILC2s was mediated via<\/em> inhibitory pathways including SHP1\/PI3K\/AKT and LAIR-1 deficiency led to exacerbated ILC2-dependent AHR in IL-33 and Alternaria alternata<\/em> models. In adoptive transfer experiments, we confirmed the LAIR-1-mediated regulation of ILC2s in vivo<\/em>. Interestingly, LAIR-1 was expressed and inducible in human ILC2s and knockdown approaches of Lair1<\/em> resulted in higher cytokine production. Finally, engagement of LAIR-1 by physiological ligand C1q, significantly reduced ILC2-dependent AHR in a humanized ILC2 murine model. <\/p>\n<\/section>\n

\n

Conclusion:<\/h3>\n

Our results unravel a novel regulatory axis in ILC2s with the capacity to reduce allergic AHR and lung inflammation.<\/p>\n<\/section>","paragraphe_en":"","documents":null},"yoast_head":"\nLAIR-1 acts as an immune checkpoint on activated ILC2s and regulates the induction of airway hyperreactivity - 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\/lair-1-acts-as-an-immune-checkpoint-on-activated-ilc2s-and-regulates-the-induction-of-airway-hyperreactivity\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"LAIR-1 acts as an immune checkpoint on activated ILC2s and regulates the induction of airway hyperreactivity - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.fr\/publication\/lair-1-acts-as-an-immune-checkpoint-on-activated-ilc2s-and-regulates-the-induction-of-airway-hyperreactivity\/\" \/>\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 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\/lair-1-acts-as-an-immune-checkpoint-on-activated-ilc2s-and-regulates-the-induction-of-airway-hyperreactivity\/\",\"url\":\"https:\/\/cri1149.fr\/publication\/lair-1-acts-as-an-immune-checkpoint-on-activated-ilc2s-and-regulates-the-induction-of-airway-hyperreactivity\/\",\"name\":\"LAIR-1 acts as an immune checkpoint on activated ILC2s and regulates the induction of airway hyperreactivity - 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