Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/54011
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dc.contributor.authorBaldan, Angel
dc.contributor.authorGonen, Ayelet
dc.contributor.authorChoung, Christina
dc.contributor.authorQue, Xuchu
dc.contributor.authorMarquart, Tyler J.
dc.contributor.authorHernandez, Irene
dc.contributor.authorBjorkhem, Ingemar
dc.contributor.authorFord, David A.
dc.contributor.authorWitztum, Joseph L.
dc.contributor.authorTarling, Elizabeth J.
dc.contributor.otherHernandez, Irene
dc.contributor.otherBjorkhem, Ingemar
dc.contributor.otherFord, David
dc.contributor.otherFord, David
dc.date.accessioned2019-02-05T13:52:37Z-
dc.date.available2019-02-05T13:52:37Z-
dc.date.issued2014
dc.identifier.issn0022-1767
dc.identifier.urihttp://hdl.handle.net/10553/54011-
dc.description.abstractMany metabolic diseases, including atherosclerosis, type 2 diabetes, pulmonary alveolar proteinosis, and obesity, have a chronic inflammatory component involving both innate and adaptive immunity. Mice lacking the ATP-binding cassette transporter G1 (ABCG1) develop chronic inflammation in the lungs, which is associated with the lipid accumulation (cholesterol, cholesterol ester, and phospholipid) and cholesterol crystal deposition that are characteristic of atherosclerotic lesions and pulmonary alveolar proteinosis. In this article, we demonstrate that specific lipids, likely oxidized phospholipids and/or sterols, elicit a lung-specific immune response in Abcg1(-/-) mice. Loss of ABCG1 results in increased levels of specific oxysterols, phosphatidylcholines, and oxidized phospholipids, including 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine, in the lungs. Further, we identify a niche-specific increase in natural Ab (NAb)-secreting B-1 B cells in response to this lipid accumulation that is paralleled by increased titers of IgM, IgA, and IgG against oxidation-specific epitopes, such as those on oxidized low-density lipoprotein and malondialdehyde-modified low-density lipoprotein. Finally, we identify a cytokine/chemokine signature that is reflective of increased B cell activation, Ab secretion, and homing. Collectively, these data demonstrate that the accumulation of lipids in Abcg1(-/-) mice induces the specific expansion and localization of B-1 B cells, which secrete NAbs that may help to protect against the development of atherosclerosis. Indeed, despite chronic lipid accumulation and inflammation, hyperlipidemic mice lacking ABCG1 develop smaller atherosclerotic lesions compared with controls. These data also suggest that Abcg(-/-) mice may represent a new model in which to study the protective functions of B-1 B cells/NAbs and suggest novel targets for pharmacologic intervention and treatment of disease.
dc.publisher0022-1767
dc.relation.ispartofJournal of Immunology
dc.sourceJournal Of Immunology[ISSN 0022-1767],v. 193 (11), p. 5637-5648
dc.subject.otherOxidation-Specific Epitopes
dc.subject.otherLow-Density-Lipoprotein
dc.subject.otherBinding Cassette Transporter
dc.subject.otherAtherosclerotic Lesions
dc.subject.otherCholesterol Efflux
dc.subject.otherApoptotic Cells
dc.subject.otherInnate Immunity
dc.subject.otherMonoclonal Autoantibodies
dc.subject.otherHematopoietic Stem
dc.subject.otherAdaptive Immunity
dc.titleABCG1 Is Required for Pulmonary B-1 B Cell and Natural Antibody Homeostasis
dc.typeinfo:eu-repo/semantics/Article
dc.typeArticle
dc.identifier.doi10.4049/jimmunol.1400606
dc.identifier.scopus84912573233
dc.identifier.isi000345443000031
dc.contributor.authorscopusid8713991200
dc.contributor.authorscopusid8726010500
dc.contributor.authorscopusid56431188000
dc.contributor.authorscopusid7003411674
dc.contributor.authorscopusid36604770200
dc.contributor.authorscopusid57201434068
dc.contributor.authorscopusid36048740000
dc.contributor.authorscopusid7401568515
dc.contributor.authorscopusid7102013646
dc.contributor.authorscopusid8883051500
dc.description.lastpage5648
dc.identifier.issue11
dc.description.firstpage5637
dc.relation.volume193
dc.type2Artículo
dc.identifier.wosWOS:000345443000031
dc.contributor.daisngid844420
dc.contributor.daisngid1359164
dc.contributor.daisngid16071999
dc.contributor.daisngid30438296
dc.contributor.daisngid1743293
dc.contributor.daisngid5207485
dc.contributor.daisngid462854
dc.contributor.daisngid14211
dc.contributor.daisngid115006
dc.contributor.daisngid9903
dc.contributor.daisngid1162101
dc.identifier.investigatorRIDN-7551-2016
dc.identifier.investigatorRIDNo ID
dc.identifier.investigatorRIDNo ID
dc.contributor.wosstandardWOS:Baldan, A
dc.contributor.wosstandardWOS:Gonen, A
dc.contributor.wosstandardWOS:Choung, C
dc.contributor.wosstandardWOS:Que, XC
dc.contributor.wosstandardWOS:Marquart, TJ
dc.contributor.wosstandardWOS:Hernandez, I
dc.contributor.wosstandardWOS:Bjorkhem, I
dc.contributor.wosstandardWOS:Ford, DA
dc.contributor.wosstandardWOS:Witztum, JL
dc.contributor.wosstandardWOS:Tarling, EJ
dc.date.coverdateDiciembre 2014
dc.identifier.ulpgces
dc.description.sjr3,716
dc.description.jcr4,922
dc.description.sjrqQ1
dc.description.jcrqQ1
dc.description.scieSCIE
item.fulltextSin texto completo-
item.grantfulltextnone-
crisitem.author.orcid0000-0001-7174-7599-
crisitem.author.fullNameHernández Hernández, Irene-
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