Expression of miRNAs miR-133b and miR-206 in the Il17a/f locus is co-regulated with IL-17 production in αβ and γδ T cells.
Expression of miRNAs miR-133b and miR-206 in the Il17a/f locus is co-regulated with IL-17 production in αβ and γδ T cells.
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DOI：
10.1371/journal.pone.0020171
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Prinz I
中科院分区：
文献类型：
--
作者：
Haas JD;Nistala K;Petermann F;Saran N;Chennupati V;Schmitz S;Korn T;Wedderburn LR;Förster R;Krueger A;Prinz I
辅助性T细胞17（Th 17）的分化是一个多步骤的过程，涉及细胞因子IL-6、TGF-β和IL-23以及IL-1β、IL-21和TNF-α。因此，产生IL-17的能力的稳健诱导涉及同线Il 17 a/f基因座的表观遗传修饰。使用近交系小鼠品系，我们鉴定了在Il 17 a/f基因座处的基因转录与附近的microRNA miR-133 b和miR-206的共调节，所述microRNA miR-133 b和miR-206聚集在Il 17 a/f上游约45 kb处。与其他CD 4 + T细胞亚群相比，这些microRNA的表达对Th 17是特异性的，这对体外极化和离体衍生的细胞同样有效。从分析的所有因素来看，IL-23是在野生型小鼠的初始CD 4 + T细胞中体外诱导miR-133 b和miR-206的最重要的细胞因子。然而，对IL-23 R缺陷小鼠的分析显示，IL-23 R信号传导对于miR-133 b和miR-206的诱导不是必需的。重要的是，我们在CCR 6+和其他易产生IL-17的γδ T细胞亚群中发现了类似的共调节。综上所述，我们发现了T细胞向产生IL-17的表型分化的新特征，该表型在αβ和γδ T细胞之间共享。值得注意的是，miR-133 b和miR-206与Il 17 a/f基因座的特异性共调节也延伸至人Th 17细胞。这使得T细胞中miR-133 b和miR-206的表达有资格作为Th 17型免疫反应的新型生物标志物。
Differentiation of T helper 17 cells (Th17) is a multistep process that involves the cytokines IL-6, TGF-β, and IL-23 as well as IL-1β, IL-21, and TNF-α. Thereby, robust induction of the capacity to produce IL-17 involves epigenetic modifications of the syntenic Il17a/f locus. Using inbred mouse strains, we identified co-regulation of gene transcription at the Il17a/f locus with the nearby microRNAs miR-133b and miR-206 that are clustered approximately 45 kb upstream of Il17a/f. Expression of these microRNAs was specific for Th17 as compared to other CD4+ T cell subsets and this was equally valid for in vitro polarized and ex vivo derived cells. From all factors analyzed, IL-23 was the most important cytokine for the in vitro induction of miR-133b and miR-206 in naive CD4+ T cells of wild type mice. However, analysis of IL-23R deficient mice revealed that IL-23R signaling was not essential for the induction of miR-133b and miR-206. Importantly, we found a similar co-regulation in CCR6+ and other γδ T cell subsets that are predisposed to production of IL-17. Taken together, we discovered a novel feature of T cell differentiation towards an IL-17-producing phenotype that is shared between αβ and γδ T cells. Notably, the specific co-regulation of miR-133b and miR-206 with the Il17a/f locus also extended to human Th17 cells. This qualifies expression of miR-133b and miR-206 in T cells as novel biomarkers for Th17-type immune reactions.
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影响因子：
30.5
作者：
Du, Changsheng;Liu, Chang;Pei, Gang
通讯作者：
Pei, Gang
DOI：
10.1083/jcb.200603008
发表时间：
2006-08-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim HK;Lee YS;Sivaprasad U;Malhotra A;Dutta A
通讯作者：
Dutta A
影响因子：
82.9
作者：
Korn, Thomas;Reddy, Jayagopala;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
DOI：
10.1073/pnas.0600666103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Chen, Zhi;Laurence, Arian;O'Shea, John J.
通讯作者：
O'Shea, John J.
影响因子：
3.3
作者：
Liu, Shih-Ping;Fu, Ru-Huei;Lin, Shinn-Zong
通讯作者：
Lin, Shinn-Zong