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Retinoic Acid Exerts Disease Stage-Dependent Effects on Pristane-Induced Lupus

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dc.contributor.authorAbdelhamid, Leilaen
dc.contributor.authorCabana-Puig, Xavieren
dc.contributor.authorSwartwout, Brianna K.en
dc.contributor.authorLee, Jiyoungen
dc.contributor.authorLi, Songen
dc.contributor.authorSun, Shaen
dc.contributor.authorLi, Yaqien
dc.contributor.authorRoss, A. Catharineen
dc.contributor.authorCecere, Thomas E.en
dc.contributor.authorLeRoith, Tanyaen
dc.contributor.authorWerre, Stephen R.en
dc.contributor.authorWang, Haifengen
dc.contributor.authorReilly, Christopher M.en
dc.contributor.authorLuo, Xin M.en
dc.date.accessioned2020-05-12T12:08:22Zen
dc.date.available2020-05-12T12:08:22Zen
dc.date.issued2020-03-20en
dc.description.abstractWe previously showed that all-trans-retinoic acid (tRA), an active metabolite of vitamin A, exacerbated pre-existing autoimmunity in lupus; however, its effects before the development of autoimmunity are unknown. Here, using a pristane-induced model, we show that tRA exerts differential effects when given at the initiation vs. continuation phase of lupus. Unlike tRA treatment during active disease, pre-pristane treatment with tRA aggravated glomerulonephritis through increasing renal expression of pro-fibrotic protein laminin beta 1, activating bone marrow conventional dendritic cells (cDCs), and upregulating the interaction of ICAM-1 and LFA-1 in the spleen, indicating an active process of leukocyte activation and trafficking. Transcriptomic analysis revealed that prior to lupus induction, tRA significantly upregulated the expression of genes associated with cDC activation and migration. Post-pristane tRA treatment, on the other hand, did not significantly alter the severity of glomerulonephritis; rather, it exerted immunosuppressive functions of decreasing circulatory and renal deposition of autoantibodies as well as suppressing the renal expression of proinflammatory cytokines and chemokines. Together, these findings suggest that tRA differentially modulate lupus-associated kidney inflammation depending on the time of administration. Interestingly, both pre- and post-pristane treatments with tRA reversed pristane-induced leaky gut and modulated the gut microbiota in a similar fashion, suggesting a gut microbiota-independent mechanism by which tRA affects the initiation vs. continuation phase of lupus.en
dc.description.notesThis work was supported by NIH grants AR067418 and AR073240.en
dc.description.sponsorshipNIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [AR067418, AR073240]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fimmu.2020.00408en
dc.identifier.issn1664-3224en
dc.identifier.other408en
dc.identifier.pmid32265909en
dc.identifier.urihttp://hdl.handle.net/10919/98226en
dc.identifier.volume11en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectretinoic aciden
dc.subjectpristane-induceden
dc.subjectlupusen
dc.subjectstage-dependenten
dc.subjectkidneyen
dc.subjectglomerulonephritisen
dc.subjectgut microbiotaen
dc.titleRetinoic Acid Exerts Disease Stage-Dependent Effects on Pristane-Induced Lupusen
dc.title.serialFrontiers in Immunologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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