{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T01:44:39Z","timestamp":1791769479967,"version":"4.3.4"},"reference-count":0,"publisher":"European Respiratory Society (ERS)","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["K12 HD047349"],"award-info":[{"award-number":["K12 HD047349"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K08 HL145098"],"award-info":[{"award-number":["K08 HL145098"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL122531"],"award-info":[{"award-number":["R01 HL122531"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL171279"],"award-info":[{"award-number":["R01 HL171279"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01 HL146002"],"award-info":[{"award-number":["U01 HL146002"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U10 HL109172"],"award-info":[{"award-number":["U10 HL109172"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2026,8,10]]},"abstract":"\n Background<\/jats:title>\n Natural killer (NK) cell dysfunction and defective inflammation resolution pathways are associated with chronic airway inflammation in asthma. NK cells are targets for regulation by essential polyunsaturated fatty acid-derived specialized pro-resolving mediators (SPMs), including resolvin D2 (RvD2), to stimulate inflammation resolution.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Multiparameter flow cytometry was utilized to examine expression patterns of select activating and inhibitory receptors, including the RvD2 receptor DRV2, on circulating NK cells in SARP3 severe and non-severe asthma subjects and healthy controls. Plasma RvD2 and serum amyloid A (SAA) was measured, and RvD2 and SAA regulation of NK cell cytotoxicity was examined\n in vitro<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Expansion of circulating NK cells with downregulated activating receptors NKp30 and NKp46 and inhibitory receptor CD161 were linked with exacerbation susceptibility and longitudinal lung function trajectory in asthma. Circulating SAA levels were higher in severe asthma patients (median 8.8\u2005\u03bcg\u00b7mL\n \u22121<\/jats:sup>\n ) than healthy individuals (2.2\u2005\u03bcg\u00b7mL\n \u22121<\/jats:sup>\n ; p=0.003). In contrast, plasma RvD2 levels were lower in severe asthma (153 pg\u00b7mL\n \u22121<\/jats:sup>\n versus<\/jats:italic>\n 208 pg\u00b7mL\n \u22121<\/jats:sup>\n in health; p=0.041), concomitant with a two-fold higher NK cell DRV2 receptor expression than in non-severe asthma subjects (3973 MFI\n versus<\/jats:italic>\n 1798; p=0.003). High-dose SAA exposure downregulated NK cell triggering receptors and resulted in a 22% suppression of cytotoxicity (48.9\u00b19.7%\n versus<\/jats:italic>\n 62.5\u00b19.2% in vehicle; p=0.001). In contrast, RvD2 enhanced NK cell cytotoxicity (38.1\u00b18.8%\n versus<\/jats:italic>\n 33.1\u00b18.3%; p=0.007) and partially reversed SAA-mediated suppression (5.4\u00b12.7% change; p=0.031).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These findings identify a perturbed counterregulatory network for inflammation resolution in severe asthma comprised of excess pro-inflammatory SAA, deficient pro-resolving RvD2, and altered NK cell immune signatures that were associated with increased asthma morbidity. The beneficial impact of RvD2 in counteracting SAA-mediated suppression of NK cell effector function supports a pivotal mechanistic role for SPMs to enhance cell-type specific resolution pathways to combat persistent airway inflammation in asthma.<\/jats:p>\n <\/jats:sec>","DOI":"10.1183\/13993003.00317-2026","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:45:17Z","timestamp":1791765917000},"page":"2600317","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulated NK cell phenotype in exacerbation-prone severe asthma"],"prefix":"10.1183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4173-3628","authenticated-orcid":false,"given":"Melody G.","family":"Duvall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison H.","family":"Dorazio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Chiha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roisin B.","family":"Reilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00efsha K.","family":"Ramdour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Krishnamoorthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Elaine","family":"Cagnina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda","family":"Phipatanakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Israel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9515-5731","authenticated-orcid":false,"given":"Bruce D.","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2026,10,11]]},"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.00317-2026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:45:17Z","timestamp":1791765917000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.00317-2026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,11]]},"references-count":0,"alternative-id":["10.1183\/13993003.00317-2026"],"URL":"https:\/\/doi.org\/10.1183\/13993003.00317-2026","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,11]]}}}