The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote T(H)17 cell-dependent emphysema.
The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote T(H)17 cell-dependent emphysema.
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DOI：
10.1038/ni.3292
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发表时间：
2015-11
影响因子：
30.5
通讯作者：
Corry DB
中科院分区：
文献类型：
--
作者：
Lu W;You R;Yuan X;Yang T;Samuel EL;Marcano DC;Sikkema WK;Tour JM;Rodriguez A;Kheradmand F;Corry DB
吸烟相关性肺气肿是一种慢性炎症性疾病，由辅助性T细胞17（TH 17）通过分子机制驱动，目前尚不清楚。在这里，我们探讨了microRNA-22（miR-22）在肺气肿中的作用。MiR-22在患有肺气肿的吸烟者的肺骨髓树突状细胞（mDC）和暴露于烟雾或纳米颗粒炭黑（nCB）的小鼠的抗原递呈细胞（APC）中通过涉及NF-κB的机制上调。MiR-22缺陷型小鼠，而不是野生型，表现出减弱的TH 17反应，并没有发展肺气肿后，暴露于烟雾或nCB。我们进一步表明，miR-22通过激活AP-1转录因子复合物和组蛋白脱乙酰酶（HDAC）4控制APC激活和TH 17反应。因此，miR-22是肺气肿和TH 17反应的关键调节剂。
Smoking-related emphysema is a chronic inflammatory disease driven by T helper 17 (TH17) cells through molecular mechanisms that remain obscure. Here we have explored the role of microRNA-22 (miR-22) in emphysema. MiR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism involving NF-κB. MiR-22-deficient mice, but not wild-type, showed attenuated TH17 responses and failed to develop emphysema after exposure to either smoke or nCB. We further show that miR-22 controls APC activation and TH17 responses through activation of AP-1 transcription factor complexes and histone deacetylase (HDAC) 4. Thus, miR-22 is a critical regulator of both emphysema and TH17 responses.