{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:39:45Z","timestamp":1789821585679,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T00:00:00Z","timestamp":1485129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15 HL112073"],"award-info":[{"award-number":["R15 HL112073"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30GM103338"],"award-info":[{"award-number":["P30GM103338"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Allergic asthma is a chronic airway inflammatory disease involving the complementary actions of innate and adaptive immune responses. Endogenously generated cannabinoids acting via <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2 receptors play important roles in both homeostatic and inflammatory processes. However, the contribution of <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2\u2010acting eicosanoids to the innate events preceding sensitization to the common house dust mite (<jats:styled-content style=\"fixed-case\">HDM<\/jats:styled-content>) allergen remains to be elucidated. We investigated the role of <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2 activation during allergen\u2010induced pulmonary inflammation and natural killer (<jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>) cell effector function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lung mucosal responses in <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2\u2010deficient (<jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2<jats:sup>\u2212\/\u2212<\/jats:sup>) mice were examined and compared with wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) littermates following intranasal exposure to <jats:styled-content style=\"fixed-case\">HDM<\/jats:styled-content> allergen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mice lacking <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2 receptors exhibited elevated numbers of pulmonary <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells yet were resistant to the induction of allergic inflammation exemplified by diminished airway eosinophilia, type 2 cytokine production and mucus secretion after allergen inhalation. This phenomenon was corroborated when <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice were treated with a <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2\u2010specific antagonist that caused a pronounced inhibition of <jats:styled-content style=\"fixed-case\">HDM<\/jats:styled-content>\u2010induced airway inflammation and goblet cell hyperplasia. Unexpectedly, the preponderance of <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells in the lungs of <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2<jats:sup>\u2212\/\u2212<\/jats:sup> mice correlated with reduced numbers of group 2 innate lymphoid cells (<jats:styled-content style=\"fixed-case\">ILC<\/jats:styled-content>2s). Depletion of <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells restored the allergen responsiveness in the lungs and was associated with elevated <jats:styled-content style=\"fixed-case\">ILC<\/jats:styled-content>2 numbers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Collectively, these results reveal that <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2 activation is crucial in regulating pulmonary <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cell function, and suggest that <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells serve to limit <jats:styled-content style=\"fixed-case\">ILC<\/jats:styled-content>2 activation and subsequent allergic airway inflammation. <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>2 inhibition may present an important target to modulate <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cell response during pulmonary inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13107","type":"journal-article","created":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T14:46:49Z","timestamp":1482158809000},"page":"937-947","source":"Crossref","is-referenced-by-count":52,"title":["<scp>CB<\/scp>2 receptors regulate natural killer cells that limit allergic airway inflammation in a murine model of asthma"],"prefix":"10.1111","volume":"72","author":[{"given":"M. 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Montana Missoula MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Stella","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Washington School of Medicine Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Sciences College of Health Professions and Biomedical Sciences University of Montana Missoula MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Jaffar","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Sciences College of Health Professions and Biomedical Sciences University of Montana Missoula MT 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