Paradoxical Effects of All-Trans-Retinoic Acid on Lupus-Like Disease in the MRL/lpr Mouse Model

Simple item page
dc.contributor.authorLiao, Xiaofengen
dc.contributor.authorRen, Jingjingen
dc.contributor.authorWei, Cheng-Hsinen
dc.contributor.authorRoss, A. Catharineen
dc.contributor.authorCecere, Thomas E.en
dc.contributor.authorJortner, Bernard S.en
dc.contributor.authorAhmed, Sattar Ansaren
dc.contributor.authorLuo, Xin M.en
dc.date.accessioned2017-01-10T21:29:21Zen
dc.date.available2017-01-10T21:29:21Zen
dc.date.issued2015-03-16en
dc.description.abstractRoles of all-trans-retinoic acid (tRA), a metabolite of vitamin A (VA), in both tolerogenic and immunogenic responses are documented. However, how tRA affects the development of systemic autoimmunity is poorly understood. Here we demonstrate that tRA have paradoxical effects on the development of autoimmune lupus in the MRL/lpr mouse model. We administered, orally, tRA or VA mixed with 10% of tRA (referred to as VARA) to female mice starting from 6 weeks of age. At this age, the mice do not exhibit overt clinical signs of lupus. However, the immunogenic environment preceding disease onset has been established as evidenced by an increase of total IgM/IgG in the plasma and expansion of lymphocytes and dendritic cells in secondary lymphoid organs. After 8 weeks of tRA, but not VARA treatment, significantly higher pathological scores in the skin, brain and lung were observed. These were accompanied by a marked increase in B-cell responses that included autoantibody production and enhanced expression of plasma cell-promoting cytokines. Paradoxically, the number of lymphocytes in the mesenteric lymph node decreased with tRA that led to significantly reduced lymphadenopathy. In addition, tRA differentially affected renal pathology, increasing leukocyte infiltration of renal tubulointerstitium while restoring the size of glomeruli in the kidney cortex. In contrast, minimal induction of inflammation with tRA in the absence of an immunogenic environment in the control mice was observed. Altogether, our results suggest that under a predisposed immunogenic environment in autoimmune lupus, tRA may decrease inflammation in some organs while generating more severe disease in others.en
dc.description.versionPublished versionen
dc.format.extent21 p.en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLiao X, Ren J, Wei C-H, Ross AC, Cecere TE, Jortner BS, et al. (2015) Paradoxical Effects of All-Trans-Retinoic Acid on Lupus-Like Disease in the MRL/lpr Mouse Model. PLoS ONE 10(3): e0118176. doi:10.1371/journal.pone.0118176en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0118176en
dc.identifier.issn1932-6203en
dc.identifier.issue3en
dc.identifier.urihttp://hdl.handle.net/10919/74225en
dc.identifier.volume10en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000351183500026&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectregulatory t-cellsen
dc.subjectintestinal dendritic cellsen
dc.subjectb-cellsen
dc.subjectvitamin-aen
dc.subjectneonatal-ratsen
dc.subjectx-receptoren
dc.subjecttgf-betaen
dc.subjectin-vitroen
dc.subjectmiceen
dc.subjecterythematosusen
dc.titleParadoxical Effects of All-Trans-Retinoic Acid on Lupus-Like Disease in the MRL/lpr Mouse Modelen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Paradoxical effects of all-trans-retinoic acid on lupus-like disease in the MRL/lpr mouse model.pdf
Size:
6.3 MB
Format:
Adobe Portable Document Format
Description:
Publisher's Version
Download
License bundle
Now showing 1 - 1 of 1
Name:
VTUL_Distribution_License_2016_05_09.pdf
Size:
18.09 KB
Format:
Adobe Portable Document Format
Description:
Download

Collections

All Faculty Deposits
Open Access Subvention Fund Articles
Scholarly Works, Virginia-Maryland College of Veterinary Medicine