{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:47:30Z","timestamp":1790740050499,"version":"4.1.0"},"reference-count":109,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Innate immune responses to allergens by airway epithelial cells (AECs) help initiate and propagate the adaptive immune response associated with allergic airway inflammation in asthma. Activation of the transcription factor NF-\u03baB in AECs by allergens or secondary mediators via G protein\u2013coupled receptors (GPCRs) is an important component of this multifaceted inflammatory cascade. Members of the caspase recruitment domain family of proteins display tissue-specific expression and help mediate NF-\u03baB activity in response to numerous stimuli. We have previously shown that caspase recruitment domain\u2013containing membrane-associated guanylate kinase protein (CARMA)3 is specifically expressed in AECs and mediates NF-\u03baB activation in these cells in response to stimulation with the GPCR agonist lysophosphatidic acid. In this study, we demonstrate that reduced levels of CARMA3 in normal human bronchial epithelial cells decreases the production of proasthmatic mediators in response to a panel of asthma-relevant GPCR ligands such as lysophosphatidic acid, adenosine triphosphate, and allergens that activate GPCRs such as Alternaria alternata and house dust mite. We then show that genetically modified mice with CARMA3-deficient AECs have reduced airway eosinophilia and proinflammatory cytokine production in a murine model of allergic airway inflammation. Additionally, we demonstrate that these mice have impaired dendritic cell maturation in the lung and that dendritic cells from mice with CARMA3-deficient AECs have impaired Ag processing. In conclusion, we show that AEC CARMA3 helps mediate allergic airway inflammation, and that CARMA3 is a critical signaling molecule bridging the innate and adaptive immune responses in the lung.<\/jats:p>","DOI":"10.4049\/jimmunol.1402983","type":"journal-article","created":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T11:15:25Z","timestamp":1433416525000},"page":"683-694","source":"Crossref","is-referenced-by-count":21,"title":["CARMA3 Is Critical for the Initiation of Allergic Airway Inflammation"],"prefix":"10.1093","volume":"195","author":[{"given":"Benjamin","family":"Causton","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"},{"name":"Division of Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravisankar A","family":"Ramadas","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josalyn L","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"},{"name":"Division of Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khristianna","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"},{"name":"Division of Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Pardo-Saganta","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"},{"name":"Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayaraj","family":"Rajagopal","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"},{"name":"Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramnik J","family":"Xavier","sequence":"additional","affiliation":[{"name":"Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"},{"name":"Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin D","family":"Medoff","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"},{"name":"Division of Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,7,15]]},"reference":[{"key":"2025030703442090600_r1","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1056\/NEJM200102013440507","article-title":"Asthma","volume":"344","author":"Busse","year":"2001","journal-title":"N. 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