Autoimmune Genetics Laboratory, VIB and University of Leuven, Leuven, Belgium.
Cell Mol Life Sci. 2012 Nov;69(21):3533-41. doi: 10.1007/s00018-012-1124-0. Epub 2012 Sep 13.
Recent research into the role of microRNA (miR) in the immune system has identified the miR-29 family as critical regulators of key processes in adaptive immunity. The miR-29 family consists of four members with shared regulatory capacity, namely miR-29a, miR-29b-1, miR-29b-2 and miR-29c. Being expressed in both T and B cells, as well as the main accessory cell types of thymic epithelium and dendritic cells, the miR-29 family has been identified as a putative regulator of immunity due to the predicted suppression of key immunological pathways. The generation of a series of in vivo molecular tools targeting the miR-29 family has identified the critical role of these miR in setting the molecular threshold for three central events in adaptive immunity: (1) control over thymic production of T cells by modulating the threshold for infection-associated thymic involution, (2) creating a neutral threshold for T cell polarization following activation, and (3) setting the threshold for B cell oncogenic transformation. These results identify the miR-29 family as potent immune modulators which have already been exploited through the evolution of a viral mimic and could potentially be exploited further for therapeutic intervention.
最近对 microRNA(miR)在免疫系统中的作用的研究表明,miR-29 家族是适应性免疫中关键过程的关键调节因子。miR-29 家族由具有共享调节能力的四个成员组成,即 miR-29a、miR-29b-1、miR-29b-2 和 miR-29c。miR-29 家族在 T 和 B 细胞以及胸腺上皮和树突状细胞的主要辅助细胞类型中表达,由于预测对关键免疫途径的抑制作用,被认为是免疫调节因子。一系列针对 miR-29 家族的体内分子工具的产生,确定了这些 miR 在设定适应性免疫三个中心事件的分子阈值方面的关键作用:(1)通过调节与感染相关的胸腺退化的感染阈值来控制胸腺中 T 细胞的产生,(2)在激活后为 T 细胞极化创建一个中性阈值,(3)为 B 细胞致癌转化设定阈值。这些结果表明,miR-29 家族是强大的免疫调节剂,它们已经通过病毒模拟物的进化得到了利用,并且可能进一步用于治疗干预。