title: Potential Inhibitory Influence of miRNA 210 on Regulatory T Cells during Epicutaneous Chemical Sensitization.
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 Tregsubsets following dermal TDI sensitization. Alterations in dLN mRNA and protein expression of Tregrelated 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 Tregsuppression 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 Tregfunction 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.
authors.affiliation: Immunology and Microbial Pathogenesis Graduate Program, West Virginia University, Morgantown, WV 26505, USA. clong14@mix.wvu.edu.|Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Allergy and Clinical Immunology Branch, Morgantown, WV 26505, USA. clong14@mix.wvu.edu.
authors.forename: Carrie Mae
authors.initials: CM
authors.lastname: Long
authors.affiliation: Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Allergy and Clinical Immunology Branch, Morgantown, WV 26505, USA. uvm3@cdc.gov.
authors.forename: Ewa
authors.initials: E
authors.lastname: Lukomska
authors.affiliation: Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Allergy and Clinical Immunology Branch, Morgantown, WV 26505, USA. nikki.marshall@inovio.com.
authors.forename: Nikki B
authors.initials: NB
authors.lastname: Marshall
authors.affiliation: Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Allergy and Clinical Immunology Branch, Morgantown, WV 26505, USA. ajay.nayak@jefferson.edu.
authors.forename: Ajay
authors.initials: A
authors.lastname: Nayak
authors.affiliation: Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Allergy and Clinical Immunology Branch, Morgantown, WV 26505, USA. dbx7@cdc.gov.
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Anderson
keywords: immunotoxicology; isocyanate; miR-210; microRNA; regulatory T cell; toluene diisocyanate