Silencing of microRNA-21 in vivo ameliorates autoimmune splenomegaly in lupus mice.
Silencing of microRNA-21 in vivo ameliorates autoimmune splenomegaly in lupus mice.
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DOI：
10.1002/emmm.201100171
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发表时间：
2011-10
影响因子：
11.1
通讯作者：
Kiriakidou, Marianthi
中科院分区：
文献类型：
--
作者：
Garchow, Barry G.;Encinas, Oscar Bartulos;Leung, Yiu Tak;Tsao, Patricia Y.;Eisenberg, Robert A.;Caricchio, Roberto;Obad, Susanna;Petri, Andreas;Kauppinen, Sakari;Kiriakidou, Marianthi
微小RNA（miRNAs）已经涉及B细胞谱系定型、T细胞分化的调节、TCR信号传导、IFN信号传导的调节和许多其它免疫过程。然而，它们在自身免疫中的功能，特别是在系统性红斑狼疮（SLE）中的功能仍然知之甚少。B6.Sle123是一种自发遗传的SLE小鼠模型，其特征为自身抗体产生、淋巴脾肿大和肾小球肾炎。我们在B6.Sle123小鼠的B和T淋巴细胞中鉴定了几种差异调节的miRNA。我们发现miR-21在狼疮B和T细胞中的表达上调，并且使用微小的种子靶向LNA在体内沉默miR-21逆转了脾肿大，脾肿大是B6. Sle 123小鼠中自身免疫的主要表现之一，并且在体内和体外去抑制PDCD 4表达。此外，用抗miR-21处理改变了CD 4/CD 8 T细胞比率，并减少了表达Fas受体的淋巴细胞群。我们的研究表明，微小的LNA可以用于有效地拮抗内源性miRNA在外周淋巴细胞在体内和体外培养的原代淋巴细胞，并可以改变小鼠的自发性遗传疾病的过程。
MicroRNAs (miRNAs) have been implicated in B cell lineage commitment, regulation of T cell differentiation, TCR signalling, regulation of IFN signalling, and numerous other immunological processes. However, their function in autoimmunity, and specifically in systemic lupus erythematosus (SLE), remains poorly understood. B6.Sle123 is a spontaneous genetic mouse model of SLE characterized by autoantibody production, lymphosplenomegaly, and glomerulonephritis. We identified several differentially regulated miRNAs in B and T lymphocytes of B6.Sle123 mice. We found that miR-21 expression in lupus B and T cells is up-regulated and that in vivo silencing of miR-21 using a tiny seed-targeting LNA reversed splenomegaly, one of the cardinal manifestations of autoimmunity in B6.Sle123 mice, and de-repressed PDCD4 expression in vivo and in vitro. In addition, treatment with anti-miR-21 altered CD4/CD8 T cell ratios and reduced Fas receptor-expressing lymphocyte populations. Our study shows that tiny LNAs can be used to efficiently antagonize endogenous miRNAs in peripheral lymphocytes in vivo and in primary lymphocytes cultured ex vivo and can alter the course of a spontaneous genetic disease in mice.
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DOI：
10.4049/jimmunol.1002218
发表时间：
2011-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Divekar AA;Dubey S;Gangalum PR;Singh RR
通讯作者：
Singh RR
影响因子：
2.6
作者：
Dai, Y.;Huang, Y-S;Yin, Y-B
通讯作者：
Yin, Y-B
DOI：
10.1073/pnas.96.24.14037
发表时间：
1999-11-23
影响因子：
11.1
作者：
Cmarik, JL;Min, HZ;Colburn, NH
通讯作者：
Colburn, NH
影响因子：
13.6
作者：
Liu, Kui;Mohan, Chandra
通讯作者：
Mohan, Chandra
全身IFN-α在B6.SLE123小鼠中驱动肾脏肾炎。
影响因子：
5.4
作者：
Fairhurst, Anna-Marie;Mathian, Alexis;Connolly, John E.;Wang, Andrew;Gray, Hillery F.;George, Tiffany A.;Boudreaux, Christopher D.;Zhou, Xin J.;Li, Quan-Zhen;Koutouzov, Sophie;Banchereau, Jacques;Wakeland, Edward K.
通讯作者：
Wakeland, Edward K.