{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:08:53Z","timestamp":1780398533876,"version":"3.54.1"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of <jats:italic>Mir223<\/jats:italic> and sphingosine-1-phosphate receptor 1 (<jats:italic>S1pr1<\/jats:italic>) in the pathogenesis of systemic lupus erythematosus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed miRNA and mRNA profiling data of CD4<jats:sup>+<\/jats:sup> splenic T cells derived from MRL\/MpJ-<jats:italic>Fas<jats:sup>lpr<\/jats:sup><\/jats:italic>\/J mice. We performed 3\u2032 untranslated region (UTR) luciferase reporter gene assay using human umbilical vein endothelial cells (HUVECs). We generated the B6-<jats:italic>Mir223<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup><jats:italic>Fas<jats:sup>lpr\/lpr<\/jats:sup><\/jats:italic> mice and the lupus phenotypes were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In CD4<jats:sup>+<\/jats:sup> splenic T cells, we identified upregulation of miR-223-3p and downregulation of the possible target, <jats:italic>S1pr1<\/jats:italic> by RNA sequencing of MRL\/MpJ-<jats:italic>Fas<jats:sup>lpr<\/jats:sup><\/jats:italic>\/J mice. The transfection with miR-223-3p mimic significantly suppressed a luciferase activity in HUVEC treated with a Lentivirus vector containing 3\u2032 UTR of <jats:italic>S1pr1<\/jats:italic>. The mRNA levels of <jats:italic>S1pr1<\/jats:italic> were significantly decreased after miR-223-3p overexpression. In B6-<jats:italic>Mir223<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup><jats:italic>Fas<jats:sup>lpr\/lpr<\/jats:sup><\/jats:italic> mice, the proportion of CD3<jats:sup>+<\/jats:sup> T cells, CD3<jats:sup>+<\/jats:sup>CD4<jats:sup>-<\/jats:sup>CD8<jats:sup>\u2212<\/jats:sup> cells, B cells, plasma cells, and S1PR1<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cells in the spleen was significantly increased compared with that in B6-<jats:italic>Mir223<\/jats:italic><jats:sup>+\/+<\/jats:sup><jats:italic>Fas<jats:sup>lpr\/lpr<\/jats:sup><\/jats:italic> mice by flow cytometry. B6-<jats:italic>Mir223<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup><jats:italic>Fas<jats:sup>lpr\/lpr<\/jats:sup><\/jats:italic> mice demonstrated the elevation of glomerular and renal vascular scores associated with enhanced intraglomerular infiltration of S1PR1<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Unexpectedly, the deletion of <jats:italic>Mir223<\/jats:italic> exacerbated the lupus phenotypes associated with increased population of S1PR1<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T in spleen and the enhanced infiltration of S1PR1<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cells in inflamed kidney tissues, suggesting compensatory role of <jats:italic>Mir223<\/jats:italic> in the pathogenesis of lupus nephritis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2020.616141","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T08:47:51Z","timestamp":1611650871000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Deletion of Mir223 Exacerbates Lupus Nephritis by Targeting S1pr1 in Faslpr\/lpr Mice"],"prefix":"10.3389","volume":"11","author":[{"given":"Sumie","family":"Hiramatsu-Asano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsue","family":"Sunahori-Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Zeggar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Katsuyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Mukai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350606","article-title":"Derivation of the SLEDAI. 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