Long Carrie Mae, Lukomska Ewa, Marshall Nikki B, Nayak Ajay, Anderson Stacey E
Immunology and Microbial Pathogenesis Graduate Program, West Virginia University, Morgantown, WV 26505, USA.
Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Allergy and Clinical Immunology Branch, Morgantown, WV 26505, USA.
Genes (Basel). 2016 Dec 27;8(1):9. doi: 10.3390/genes8010009.
Toluene diisocyanate (TDI) is a potent low molecular weight chemical sensitizer and a leading cause of chemical-induced occupational asthma. The regulatory potential of microRNAs (miRNAs) has been recognized in a variety of disease states, including allergic disease; however, the roles of miRNAs in chemical sensitization are largely unknown. In a previous work, increased expression of multiple miRNAs during TDI sensitization was observed and several putative mRNA targets identified for these miRNAs were directly related to regulatory T-cell (T) differentiation and function including Foxp3 and Runx3. In this work, we show that miR-210 expression is increased in the mouse draining lymph node (dLN) and T subsets following dermal TDI sensitization. Alterations in dLN mRNA and protein expression of T related genes/putative miR-210 targets (foxp3, runx3, ctla4, and cd25) were observed at multiple time points following TDI exposure and in ex vivo systems. A T suppression assay, including a miR-210 mimic, was utilized to investigate the suppressive ability of T. Cells derived from TDI sensitized mice treated with miR-210 mimic had less expression of miR-210 compared to the acetone control suggesting other factors, such as additional miRNAs, might be involved in the regulation of the functional capabilities of these cells. These novel findings indicate that miR-210 may have an inhibitory role in T function during TDI sensitization. Because the functional roles of miRNAs have not been previously elucidated in a model of chemical sensitization, these data contribute to the understanding of the potential immunologic mechanisms of chemical induced allergic disease.
甲苯二异氰酸酯（TDI）是一种强效的低分子量化学致敏剂，也是化学诱导职业性哮喘的主要病因。微小RNA（miRNA）的调控潜力已在包括过敏性疾病在内的多种疾病状态中得到认可；然而，miRNA在化学致敏中的作用在很大程度上尚不清楚。在之前的一项研究中，观察到TDI致敏过程中多种miRNA表达增加，并且鉴定出的这些miRNA的几个假定mRNA靶标与调节性T细胞（Treg）的分化和功能直接相关，包括Foxp3和Runx3。在本研究中，我们发现经皮肤TDI致敏后，小鼠引流淋巴结（dLN）和T细胞亚群中miR-210表达增加。在TDI暴露后的多个时间点以及体外系统中，观察到dLN中Treg相关基因/假定的miR-210靶标（foxp3、runx3、ctla4和cd25）的mRNA和蛋白质表达发生改变。采用包括miR-210模拟物在内的Treg抑制试验来研究Treg的抑制能力。与丙酮对照组相比，用miR-210模拟物处理的TDI致敏小鼠来源的细胞中miR-210表达较低，这表明其他因素（如其他miRNA）可能参与了这些细胞功能能力的调节。这些新发现表明，miR-210在TDI致敏过程中可能对Treg功能具有抑制作用。由于此前尚未在化学致敏模型中阐明miRNA的功能作用，这些数据有助于理解化学诱导过敏性疾病的潜在免疫机制。
