MiR-34a promotes DCs development and inhibits their function on T cell activation by targeting WNT1.
MiR-34a promotes DCs development and inhibits their function on T cell activation by targeting WNT1.
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MiR-34a 通过靶向 WNT1 促进 DC 发育并抑制其对 T 细胞激活的功能
DOI：
10.18632/oncotarget.15228
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发表时间：
2017-03-07
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
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作者：
Huang A;Yang Y;Chen S;Xia F;Sun D;Fang D;Xiong S;Jin L;Zhang J
MicroRNAs在许多生物过程中起着重要的作用。microrna是否也作用于树突状细胞（DC）的分化和功能尚不清楚。在这项研究中，在过表达miR-34a的骨髓嵌合和转基因（TG）小鼠中，常规dc （cdc）和浆细胞样dc （pDCs）均增加。进一步的实验表明，miR-34a促进preDC分化为cdc和pDCs，但不影响dc的增殖和凋亡。荧光素酶报告实验和Western blot实验表明WNT1是dc中miR-34a的直接靶点。有趣的是，过表达miR-34a的cdc也会产生大量IL-17a，由于抑制TCF1表达而抑制T细胞活化，从而增加RORγT表达。综上所述，miR-34a促进preDC分化为cDCs和pDCs，并通过产生IL-17a抑制cDCs激活CD4+ T细胞的功能。
MicroRNAs serve important functions in numerous biological processes. Whether microRNAs also act on dendritic cell (DC) differentiation and function remains unclear. In this study, both conventional DCs (cDCs) and plasmacytoid DCs (pDCs) were increased in miR-34a overexpressing bone marrow chimeric and transgenic (TG) mice. Further experiments showed that miR-34a promoted preDC differentiated into cDCs and pDCs without affecting the proliferation and apoptosis of DCs. Luciferase report assay and Western blot experiments demonstrated that WNT1 is the direct target of miR-34a in DCs. Interestingly, miR-34a overexpressing cDCs also produced a large amount of IL-17a and suppressed T cell activation because of the inhibition of TCF1 expression, thus increasing RORγT expression. Taken together, miR-34a promotes preDC to differentiate into cDCs and pDCs, as well as inhibits the function of cDCs on the activation of CD4+ T cells by producing IL-17a.