Abstract
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 (Treg) 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 Treg subsets following dermal TDI sensitization. Alterations in dLN mRNA and protein expression of Treg 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 Treg suppression assay, including a miR-210 mimic, was utilized to investigate the suppressive ability of Tregs. 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 Treg 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.
Highlights
Occupational allergic disease is a significant health burden
The kinetics of mature miR-210 expression were investigated via RT-PCR in the draining lymph node (dLN) following
As previously reported [1], dLN miR-210 increased at various time points during 0.5% and 4% Toluene diisocyanate (TDI) sensitization, including four (4%), seven, and nine (0.5% and 4%)
Summary
Occupational allergic disease is a significant health burden. Diisocyanates are a group of highly reactive chemicals characterized by the presence of double isocyanate functional groups; many of these chemicals are potent sensitizers and major causative agents of occupational allergic disease [2,3,4]. The principal routes of human exposure to TDI are inhalation and dermal contact [6] and sensitization leading to allergic disease has been documented for both routes [7,10]. Because of the occupational significance of and lack of validated identification strategies for chemical respiratory sensitizers like TDI [4,11], it is necessary to investigate and identify functional pathways and mechanisms that are involved in TDI sensitization
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