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Interleukin 6 Accelerates Mortality by Promoting the Progression of the Systemic Lupus Erythematosus-Like Disease of BXSB. Yaa Mice

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dc.contributor.authorJain, Shwetaen
dc.contributor.authorPark, Giljunen
dc.contributor.authorSproule, Thomas J.en
dc.contributor.authorChristianson, Gregory J.en
dc.contributor.authorLeeth, Caroline M.en
dc.contributor.authorWang, Hongshengen
dc.contributor.authorRoopenian, Derry C.en
dc.contributor.authorMorse, Herbert C. IIIen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2017-07-28T18:37:30Zen
dc.date.available2017-07-28T18:37:30Zen
dc.date.issued2016-04-06en
dc.description.abstractIL6 is a multifunctional cytokine that drives terminal B cell differentiation and secretion of immunoglobulins. IL6 also cooperates with IL21 to promote differentiation of CD4+ T follicular helper cells (TFH). Elevated serum levels of IL6 correlate with disease flares in patients with systemic lupus erythematosus (SLE). We previously reported that IL21 produced by TFH plays a critical role in the development of the SLE-like disease of BXSB.Yaa mice. To examine the possible contributions of IL6 to disease, we compared disease parameters in IL6-deficient and IL6-competent BXSB.Yaa mice. We report that survival of IL6-deficient BXSB.Yaa mice was significantly prolonged in association with significant reductions in a variety of autoimmune manifestations. Moreover, B cells stimulated by co-engagement of TLR7 and B cell receptor (BCR) produced high levels of IL6 that was further augmented by stimulation with Type I interferon (IFN1). Importantly, the frequencies of TFH and serum levels of IL21 were significantly reduced in IL6-deficient mice. These findings suggest that high-level production of IL6 by B cells induced by integrated signaling from the IFN1 receptor, TLR7 and BCR promotes the differentiation of IL21-secreting TFH in a signaling sequence that drives the lethal autoimmune disease of BXSB.Yaa mice.en
dc.description.versionPublished versionen
dc.format.extent? - ? (19) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0153059en
dc.identifier.issn1932-6203en
dc.identifier.issue4en
dc.identifier.orcidLeeth, CM [0000-0002-5909-7623]en
dc.identifier.urihttp://hdl.handle.net/10919/78464en
dc.identifier.volume11en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000373603500090&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons CC0 1.0 Universal Public Domain Dedicationen
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/en
dc.subjectcd4(+) t-cellsen
dc.subjecttoll-like receptorsen
dc.subjectactivate b-cellsen
dc.subjectmurine lupusen
dc.subjectanti-dnaen
dc.subjectin-vivoen
dc.subjectil-6en
dc.subjecttlr7en
dc.subjectdifferentiationen
dc.subjectexpressionen
dc.titleInterleukin 6 Accelerates Mortality by Promoting the Progression of the Systemic Lupus Erythematosus-Like Disease of BXSB. Yaa Miceen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Animal and Poultry Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen

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