Deletion of Mir223 Exacerbates Lupus Nephritis by Targeting S1pr1 in Fas(lpr/lpr) Mice.
Deletion of Mir223 Exacerbates Lupus Nephritis by Targeting S1pr1 in Fas(lpr/lpr) Mice.
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DOI：
10.3389/fimmu.2020.616141
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发表时间：
2020
影响因子：
7.3
通讯作者：
Wada J
中科院分区：
文献类型：
--
作者：
Hiramatsu-Asano S;Sunahori-Watanabe K;Zeggar S;Katsuyama E;Mukai T;Morita Y;Wada J
微小RNA（miRNAs）及其靶mRNA在各种免疫介导的细胞中差异表达。在这里，我们研究了Mir 223和鞘氨醇-1-磷酸受体1（S1 pr 1）在系统性红斑狼疮发病机制中的作用。我们分析了来自MRL/MpJ-Faslpr/J小鼠的CD 4+脾T细胞的miRNA和mRNA谱数据。我们用人脐静脉内皮细胞（HUVECs）进行了3′非翻译区（UTR）荧光素酶报告基因检测。我们产生了B6-Mir 223 −/−Faslpr/lpr小鼠，并分析了狼疮表型。在CD 4+脾T细胞中，我们通过MRL/MpJ-Faslpr/J小鼠的RNA测序鉴定了miR-223- 3 p的上调和可能的靶点S1 pr 1的下调。miR-223- 3 p模拟物转染显著抑制了用含有S1 pr 1的3′ UTR的慢病毒载体处理的HUVEC中的荧光素酶活性。miR-223- 3 p过表达后S1 pr 1 mRNA水平显著降低。在B6-Mir 223 −/−Faslpr/lpr小鼠中，与B6-Mir 223 +/+Faslpr/lpr小鼠相比，通过流式细胞术，脾脏中的CD 3 + T细胞、CD 3 + CD 4-CD 8 −细胞、B细胞、浆细胞和S1 PR 1 + CD 4 + T细胞的比例显著增加。B6-Mir 223 −/−Faslpr/lpr小鼠表现出肾小球和肾血管评分升高，与肾小球内S1 PR 1 + CD 4 + T细胞浸润增强相关。出乎意料的是，Mir 223的缺失加剧了狼疮表型，与脾脏中S1 PR 1 + CD 4 + T细胞数量增加和炎症肾组织中S1 PR 1 + CD 4 + T细胞浸润增强相关，表明Mir 223在狼疮肾炎发病机制中的代偿作用。
The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of Mir223 and sphingosine-1-phosphate receptor 1 (S1pr1) in the pathogenesis of systemic lupus erythematosus. We analyzed miRNA and mRNA profiling data of CD4+ splenic T cells derived from MRL/MpJ-Faslpr/J mice. We performed 3′ untranslated region (UTR) luciferase reporter gene assay using human umbilical vein endothelial cells (HUVECs). We generated the B6-Mir223−/−Faslpr/lpr mice and the lupus phenotypes were analyzed. In CD4+ splenic T cells, we identified upregulation of miR-223-3p and downregulation of the possible target, S1pr1 by RNA sequencing of MRL/MpJ-Faslpr/J mice. The transfection with miR-223-3p mimic significantly suppressed a luciferase activity in HUVEC treated with a Lentivirus vector containing 3′ UTR of S1pr1. The mRNA levels of S1pr1 were significantly decreased after miR-223-3p overexpression. In B6-Mir223−/−Faslpr/lpr mice, the proportion of CD3+ T cells, CD3+CD4-CD8− cells, B cells, plasma cells, and S1PR1+CD4+ T cells in the spleen was significantly increased compared with that in B6-Mir223+/+Faslpr/lpr mice by flow cytometry. B6-Mir223−/−Faslpr/lpr mice demonstrated the elevation of glomerular and renal vascular scores associated with enhanced intraglomerular infiltration of S1PR1+CD4+ T cells. Unexpectedly, the deletion of Mir223 exacerbated the lupus phenotypes associated with increased population of S1PR1+CD4+ T in spleen and the enhanced infiltration of S1PR1+CD4+ T cells in inflamed kidney tissues, suggesting compensatory role of Mir223 in the pathogenesis of lupus nephritis.
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DOI：
10.1016/j.clim.2016.04.010
发表时间：
2017-12
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Koga T;Ichinose K;Tsokos GC
通讯作者：
Tsokos GC
影响因子：
4.6
作者：
Aoki M;Aoki H;Ramanathan R;Hait NC;Takabe K
通讯作者：
Takabe K
影响因子：
2.6
作者：
Chen, D-Y;Chen, Y-M;Lan, J-L
通讯作者：
Lan, J-L
影响因子：
82.9
作者：
Chimen M;McGettrick HM;Apta B;Kuravi SJ;Yates CM;Kennedy A;Odedra A;Alassiri M;Harrison M;Martin A;Barone F;Nayar S;Hitchcock JR;Cunningham AF;Raza K;Filer A;Copland DA;Dick AD;Robinson J;Kalia N;Walker LSK;Buckley CD;Nash GB;Narendran P;Rainger GE
通讯作者：
Rainger GE
影响因子：
64.8
作者：
Johnnidis, Jonathan B.;Harris, Marian H.;Camargo, Fernando D.
通讯作者：
Camargo, Fernando D.