Altered miRNA expression in T regulatory cells in course of multiple sclerosis
Altered miRNA expression in T regulatory cells in course of multiple sclerosis
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DOI：
10.1016/j.jneuroim.2010.06.009
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发表时间：
2010-09-14
影响因子：
3.3
通讯作者：
Granieri, Enrico
中科院分区：
文献类型：
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作者：
De Santis, Giuseppe;Ferracin, Manuela;Granieri, Enrico
目的：多发性硬化症(MS)是一种针对中枢神经系统成分的慢性炎症反应。已知调节性T细胞(Tregs)在自身免疫平衡中起关键作用，其不适当的功能可能促进自身侵袭性T细胞克隆的扩张。近年来，microRNAs(MiRNAs)参与了自身免疫性疾病，其在免疫细胞中的功能丧失被证明促进了全身性自身免疫性疾病。在这里，我们分析了来自MS-RR的Treg细胞的miRNA表达谱。方法：我们通过微阵列分析12例MS复发缓解期患者和14名健康对照的CD4(+)CD25(+High)T细胞的miRNA全基因组表达谱。由于CD4(+)CD25(+High)T细胞包括T调节细胞(CD4(+)CD25(+High)CD127(dim/-))和T效应细胞(CD4(+)CD25(+High)CD127(+))，我们对从同一血液样本中分离的CD4(+)CD25(+High)CD127(dim/-)和CD4(+)CD25(+High)CD127(+)细胞进行了定量RT-PCR。结果：我们发现23个人类miRNAs在MS患者和健康献血者的CD4(+)CD25(+High)真Treg细胞中存在差异表达在解除调节的miRNAs中，与健康献血者相比，MS患者中的miR-106b-25成员的CD4(+)CD25(高)CD127(dim/-)T调节细胞的表达下调。结论：MIR-106b和miR-25通过作用于CDKN1A/p21和BCL2L11/Bim调控转化生长因子-β信号通路。转化生长因子-β参与调节T细胞的分化和成熟。因此，这个miRNA簇的解除调控可能通过改变转化生长因子-β的生物学功能来改变MS过程中Treg细胞的活性。(C)2010爱思唯尔B.V.保留所有权利。
Objectives: Multiple sclerosis (MS) is a chronic inflammatory response against constituents of the central nervous system. It is known that regulatory T cells (Tregs) play a key role in the autoimmune balance and their improper function may facilitate the expansion of autoaggressive T cell clones. Recently, microRNAs (miRNAs) have been involved in autoimmune disorders and their loss-of-function in immune cells was shown to facilitate systemic autoimmune disorders. Here, we analyzed the miRNA expression profile in Tregs from MS-RR.Methods: We assessed miRNA genome-wide expression profile by microarray analysis on CD4(+)CD25(+high) T cells from 12 MS relapsing-remitting patients in stable condition and 14 healthy controls. Since CD4(+)CD25(+high) T cells comprise both T regulatory cells (CD4(+)CD25(+high)CD127(dim/-)) and T effector cells (CD4(+)CD25(+high)CD127(+)), we performed a quantitative RT-PCR on CD4(+)CD25(+high)CD127(dim/-) and CD4(+)CD25(+high)CD127(+) cells isolated from the same blood sample.Results: We found 23 human miRNAs differentially expressed between CD4(+)CD25(+high) bona fide Treg cells from MS patients vs. healthy donors, but, conversely, among the deregulated miRNAs, members of the miR-106b-25 were found down-regulated in MS patients when compared to healthy donors in CD4(+)CD25(high)CD127(dim/-) T regulatory cells. More interesting, the ratio between Tregfieff showed an enrichment of these microRNA in T regulatory cells derived from patients if compared to healthy controls.Conclusion: miR-106b and miR-25 were previously shown to modulate the TGF-beta signaling pathway through their action on CDKN1A/p21 and BCL2L11/Bim. TGF-beta is involved in T regulatory cells differentiation and maturation. Therefore, the deregulation of this miRNA cluster may alter Treg cells activity in course of MS, by altering TGF-beta, biological functions. (C) 2010 Elsevier B.V. All rights reserved.