Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210.
Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210.
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microRNA-210（miR-210）是缺氧的标志性microRNA。我们发现活化T细胞中miR-210丰度的稳健增加（>100倍），特别是在TH 17谱系中。缺氧与T细胞受体（TCR）-CD 28刺激协同作用，以加速和增加Mir 210表达的幅度。Mir 210直接受HIF-1α调节，HIF-1 α是TH 17极化的关键调节因子。令人惊讶的是，Hif 1a被鉴定为miR-210靶点，表明miR-210抑制HIF-1α蛋白表达的负反馈。Mir 210的缺失在低氧条件下促进了TH 17的分化。在实验性结肠炎中，miR-210降低了Hif 1a转录物的丰度，降低了产生炎性细胞因子的细胞比例，并控制了疾病的严重程度。我们的研究将miR-210鉴定为缺氧中T细胞分化的重要调节因子，这可以限制免疫病理学。
MicroRNA-210 (miR-210) is a signature microRNA of hypoxia. We found robust increase (>100-fold) of miR-210 abundance in activated T cells, especially in the TH17 lineage. Hypoxia synergized with T cell receptor (TCR)–CD28 stimulation to accelerate and increase the magnitude of Mir210 expression. Mir210 was directly regulated by HIF-1α, a key regulator of TH17 polarization. Surprisingly, Hif1a was identified as a miR-210-target, suggesting negative-feedback by miR-210 to inhibit HIF-1α protein expression. Deletion of Mir210 promoted TH17 differentiation under conditions with limited oxygen. In experimental colitis, miR-210 reduced Hif1a transcript abundance, reduced the proportion of cells producing inflammatory cytokines and controlled disease severity. Our study identifies miR-210 as an important regulator of T cell differentiation in hypoxia, which can limit immunopathology.
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影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
16
作者：
Leung AK;Sharp PA
通讯作者：
Sharp PA
影响因子：
3.7
作者：
Favaro E;Ramachandran A;McCormick R;Gee H;Blancher C;Crosby M;Devlin C;Blick C;Buffa F;Li JL;Vojnovic B;Pires das Neves R;Glazer P;Iborra F;Ivan M;Ragoussis J;Harris AL
通讯作者：
Harris AL
DOI：
10.1038/nri3494
发表时间：
2013-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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影响因子：
10.5
作者：
Chong, Mark M. W.;Zhang, Guoan;Littman, Dan R.
通讯作者：
Littman, Dan R.