Lu Wen, You Ran, Yuan Xiaoyi, Yang Tianshu, Samuel Errol L G, Marcano Daniela C, Sikkema William K A, Tour James M, Rodriguez Antony, Kheradmand Farrah, Corry David B
Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas, USA.
Translational Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, Texas, USA.
Nat Immunol. 2015 Nov;16(11):1185-94. doi: 10.1038/ni.3292. Epub 2015 Oct 5.
Smoking-related emphysema is a chronic inflammatory disease driven by the T(H)17 subset of helper T cells through molecular mechanisms that remain obscure. Here we explored the role of the microRNA miR-22 in emphysema. We found that 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 that involved the transcription factor NF-κB. Mice deficient in miR-22, but not wild-type mice, showed attenuated T(H)17 responses and failed to develop emphysema after exposure to smoke or nCB. We further found that miR-22 controlled the activation of APCs and T(H)17 responses through the activation of AP-1 transcription factor complexes and the histone deacetylase HDAC4. Thus, miR-22 is a critical regulator of both emphysema and T(H)17 responses.
吸烟相关的肺气肿是一种慢性炎症性疾病，由辅助性T细胞的T(H)17亚群通过仍不清楚的分子机制驱动。在此，我们探究了微小RNA miR-22在肺气肿中的作用。我们发现，miR-22在患有肺气肿的吸烟者的肺髓样树突状细胞（mDC）以及暴露于香烟烟雾或纳米颗粒炭黑（nCB）的小鼠的抗原呈递细胞（APC）中通过涉及转录因子NF-κB的机制上调。缺乏miR-22的小鼠而非野生型小鼠，在暴露于香烟烟雾或nCB后，T(H)17反应减弱且未发生肺气肿。我们进一步发现，miR-22通过激活AP-1转录因子复合物和组蛋白脱乙酰酶HDAC4来控制APC的激活和T(H)17反应。因此，miR-22是肺气肿和T(H)17反应的关键调节因子。
