Anti-C1q antibodies as a diagnostic marker of proliferative lupus nephritis: comment on the article by Katsumata et al.
Anti-C1q antibodies as a diagnostic marker of proliferative lupus nephritis: comment on the article by Katsumata et al.
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DOI：
10.1002/art.33384
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发表时间：
2012
影响因子：
--
通讯作者：
M. Trendelenburg
中科院分区：
文献类型：
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作者：
M. Trendelenburg
越来越多的证据表明，miRNAs在免疫细胞的发育以及先天性和适应性免疫应答的微调中起着非常重要的作用。众所周知，单个miRNA可以调控数百至数千个靶基因，并且单个人类基因可以被数百个miRNA调控。据估计，人类基因中至少有三分之一的基因可能受到miRNAs的调控。miRNA的丰富和普遍存在的性质为开发用于炎性疾病（包括SLE）的新的治疗干预提供了机会和挑战（1，2）。已经确定miR-146 a是免疫细胞功能的重要负调节剂（3），并且最近报道miR-146 a敲除小鼠显示外周T细胞耐受性丧失、大量骨髓增殖，肿瘤的发展（4）。Lu及其同事证实，miR-146 a控制Treg细胞抑制功能和Treg细胞介导的Th 1应答调节的特定方面（5）。然而，在类风湿性关节炎（RA）的研究中，与健康对照相比，miR-146 a在患者的滑膜成纤维细胞、外周血单核细胞（PBMC）、滑液、PBMC衍生的CD 4 T细胞和Th 17细胞中一致上调;值得关注的是，TRAF 6和IRAK 1（miR-146 a的靶基因）的表达在RA患者和健康个体之间没有差异（6）。这些数据表明，miR-146 a在免疫调节中具有不同的作用，并且其在不同疾病中的作用也可能相当不同。因此，在设计基于机制的方法来操纵个体疾病情况下的miR-146表达时应非常小心。早发性动脉粥样硬化患者的病因
There is accumulating evidence indicating that miRNAs play very important roles in the development of immune cells and in fine-turning the innate and adaptive immune responses. It is well known that a single miRNA can regulate hundreds to more than thousands of target genes, and that a single human gene can be regulated by hundreds of miRNAs. The proportion of human genes that are probably regulated by miRNAs has been estimated to be at least one-third. The abundance and ubiquitous nature of miRNAs offer opportunities and challenges in the development of novel therapeutic interventions for inflammatory diseases, including SLE (1, 2).It has been established that miR-146a is an important negative regulator of immune cell function (3), and it was recently reported that miR-146a–knockout mice display a loss of peripheral T cell tolerance, massive myeloproliferation, and tumor development (4). Lu and colleagues confirmed that miR-146a controls specific aspects of Treg cell suppressor function and Treg cell–mediated regulation of Th1 responses (5). However, in studies of rheumatoid arthritis (RA), miR-146a has been shown to be consistently up-regulated in synovial fibroblasts, peripheral blood mononuclear cells (PBMCs), synovial fluid, PBMC-derived CD4 T cells, and Th17 cells from patients compared with healthy controls; of interest, expression of TRAF6 and IRAK1, target genes of miR-146a, did not differ between RA patients and healthy individuals (6). These data suggest that miR-146a has diverse effects in immune regulation and its roles in different diseases may also be quite different. Therefore, great care should be taken in designing a mechanism-based approach to the manipulation of miR-146 expression in individual disease situations. The etiology of premature atherosclerosis in patients