Dynamic modulation of thymic microRNAs in response to stress.
Dynamic modulation of thymic microRNAs in response to stress.
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DOI：
10.1371/journal.pone.0027580
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
van Oers NS
中科院分区：
文献类型：
--
作者：
Belkaya S;Silge RL;Hoover AR;Medeiros JJ;Eitson JL;Becker AM;de la Morena MT;Bassel-Duby RS;van Oers NS
生理应激引起先天和适应性免疫反应的快速变化。胸腺中发育的未成熟αβ T细胞对应激特别敏感，感染和/或暴露于脂多糖或糖皮质激素会引发快速的凋亡程序。microrna是一类小的非编码rna，通过靶向不同mrna进行降解来调节全球基因表达。我们假设胸腺编码的microRNAs的一个子集可能是应激反应和调节胸腺功能。我们对从小鼠胸腺组织中分离的对照或应激胸腺组织进行了microRNA谱分析。我们鉴定出18个microrna在脂多糖或合成皮质类固醇地塞米松作用下发生1.5倍的失调。其中包括具有抗凋亡功能的miR-17-90簇和有助于T细胞耐受的miR-181家族。应激诱导的胸腺microrna的变化在CD4−CD8−、CD4+CD8+、CD4+CD8−和CD4−CD8+胸腺细胞亚群中受到动态和明显的调节。几种不同调节的小鼠胸腺mir在心脏、肾脏、肝脏、大脑和/或脾脏中也有应激反应。最显著的胸腺microRNA下调是miR-181d，在应激后表现出15倍的减少。该miR与miR-181家族的另一成员miR-181a具有相似和不同的基因靶点。许多差异调节的microrna在胸腺生成中具有已知的功能，表明它们的失调将改变T细胞库的选择和naïve T细胞的形成。该数据对抗炎类固醇、消融术等临床治疗具有启示意义，并为感染的后果提供了机制见解。
Physiological stress evokes rapid changes in both the innate and adaptive immune response. Immature αβ T cells developing in the thymus are particularly sensitive to stress, with infections and/or exposure to lipopolysaccharide or glucocorticoids eliciting a rapid apoptotic program. MicroRNAs are a class of small, non-coding RNAs that regulate global gene expression by targeting diverse mRNAs for degradation. We hypothesized that a subset of thymically encoded microRNAs would be stress responsive and modulate thymopoiesis. We performed microRNA profiling of thymic microRNAs isolated from control or stressed thymic tissue obtained from mice. We identified 18 microRNAs that are dysregulated >1.5-fold in response to lipopolysaccharide or the synthetic corticosteroid dexamethasone. These included the miR-17-90 cluster, which have anti-apoptotic functions, and the miR-181 family, which contribute to T cell tolerance. The stress-induced changes in the thymic microRNAs are dynamically and distinctly regulated in the CD4−CD8−, CD4+CD8+, CD4+CD8−, and CD4−CD8+ thymocyte subsets. Several of the differentially regulated murine thymic miRs are also stress responsive in the heart, kidney, liver, brain, and/or spleen. The most dramatic thymic microRNA down modulated is miR-181d, exhibiting a 15-fold reduction following stress. This miR has both similar and distinct gene targets as miR-181a, another member of miR-181 family. Many of the differentially regulated microRNAs have known functions in thymopoiesis, indicating that their dysregulation will alter T cell repertoire selection and the formation of naïve T cells. This data has implications for clinical treatments involving anti-inflammatory steroids, ablation therapies, and provides mechanistic insights into the consequences of infections.
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影响因子：
16
作者：
Leung AK;Sharp PA
通讯作者：
Sharp PA
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
9.8
作者：
John B;Enright AJ;Aravin A;Tuschl T;Sander C;Marks DS
通讯作者：
Marks DS
影响因子：
30.8
作者：
Krek, A;Grun, D;Rajewsky, N
通讯作者：
Rajewsky, N
DOI：
10.1073/pnas.95.25.14909
发表时间：
1998-12-08
影响因子：
11.1
作者：
DeJarnette, JB;Sommers, CL;Love, PE
通讯作者：
Love, PE