{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:10:26Z","timestamp":1779243026525,"version":"3.51.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"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":[[2012,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mice with genetic deletion of the cholesterol transporter ATP binding cassette G1 (ABCG1) have pulmonary lipidosis and enhanced innate immune responses in the airway. Whether ABCG1 regulates adaptive immune responses to the environment is unknown. To this end, Abcg1+\/+ and Abcg1\u2212\/\u2212 mice were sensitized to OVA via the airway using low-dose LPS as an adjuvant, and then challenged with OVA aerosol. Naive Abcg1\u2212\/\u2212 mice displayed increased B cells, CD4+ T cells, CD8+ T cells, and dendritic cells (DCs) in lung and lung-draining mediastinal lymph nodes, with lung CD11b+ DCs displaying increased CD80 and CD86. Upon allergen sensitization and challenge, the Abcg1\u2212\/\u2212 airway, compared with Abcg1+\/+, displayed reduced Th2 responses (IL-4, IL-5, eosinophils), increased neutrophils and IL-17, but equivalent airway hyperresponsiveness. Reduced Th2 responses were also found using standard i.p. OVA sensitization with aluminum hydroxide adjuvant. Mediastinal lymph nodes from airway-sensitized Abcg1\u2212\/\u2212 mice produced reduced IL-5 upon ex vivo OVA challenge. Abcg1\u2212\/\u2212 CD4+ T cells displayed normal ex vivo differentiation, whereas Abcg1\u2212\/\u2212 DCs were found paradoxically to promote Th2 polarization. Th17 cells, IL-17+ \u03b3\u03b4T cells, and IL-17+ neutrophils were all increased in Abcg1\u2212\/\u2212 lungs, suggesting Th17 and non-Th17 sources of IL-17 excess. Neutralization of IL-17 prior to challenge normalized eosinophils and reduced neutrophilia in the Abcg1\u2212\/\u2212 airway. We conclude that Abcg1\u2212\/\u2212 mice display IL-17\u2013mediated suppression of eosinophilia and enhancement of neutrophilia in the airway following allergen sensitization and challenge. These findings identify ABCG1 as a novel integrator of cholesterol homeostasis and adaptive immune programs.<\/jats:p>","DOI":"10.4049\/jimmunol.1101605","type":"journal-article","created":{"date-parts":[[2012,4,27]],"date-time":"2012-04-27T00:31:11Z","timestamp":1335486671000},"page":"5327-5336","source":"Crossref","is-referenced-by-count":31,"title":["ATP Binding Cassette Transporter G1 Deletion Induces IL-17\u2013Dependent Dysregulation of Pulmonary Adaptive Immunity"],"prefix":"10.1093","volume":"188","author":[{"given":"David W","family":"Draper","sequence":"first","affiliation":[{"name":"Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , Research Triangle Park, NC 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kymberly M","family":"Gowdy","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory 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27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory S","family":"Whitehead","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , Research Triangle Park, NC 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Nakano","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , Research Triangle Park, NC 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun R","family":"Pandiri","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , Research Triangle Park, NC 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie F","family":"Foley","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , Research Triangle Park, NC 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan T","family":"Remaley","sequence":"additional","affiliation":[{"name":"Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald N","family":"Cook","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory 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Med."},{"key":"2025032410113028500_r21","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1164\/rccm.200911-1775OC","article-title":"Resolution of allergic airway inflammation and airway hyperreactivity is mediated by IL-17-producing \u03b3\u03b4T cells","volume":"182","author":"Murdoch","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025032410113028500_r22","doi-asserted-by":"crossref","first-page":"6117","DOI":"10.4049\/jimmunol.181.9.6117","article-title":"IL-17-producing alveolar macrophages mediate allergic lung inflammation related to asthma","volume":"181","author":"Song","year":"2008","journal-title":"J. Immunol."},{"key":"2025032410113028500_r23","doi-asserted-by":"crossref","first-page":"6908","DOI":"10.4049\/jimmunol.165.12.6908","article-title":"Costimulation light: activation of CD4+ T cells with CD80 or CD86 rather than anti-CD28 leads to a Th2 cytokine profile","volume":"165","author":"Broeren","year":"2000","journal-title":"J. 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Care Med."},{"key":"2025032410113028500_r41","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1161\/01.ATV.0000148707.93054.7d","article-title":"Statins inhibit synthesis of an oxysterol ligand for the liver X receptor in human macrophages with consequences for cholesterol flux","volume":"24","author":"Wong","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. 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