The immunomodulatory potential of microRNA 210 and regulatory T cells in a murine model of chemical sensitization

Details

• Personal Author:
  Anderson S ; Long CM ; Lukomska E ; Marshall N ; Meade BJ ; Shane H ; Siegel P
• Description:
  Toluene 2,4-diisocyanate (TDI) is a low molecular weight chemical sensitizer and a major cause of occupational asthma. The roles of immunomodulatory elements such as microRNAs, which alter gene expression, and regulatory T cells (Tregs), which suppress T cell-mediated responses, in TDI sensitization are unknown. We have previously shown that miR- 210 expression in the draining lymph node (dLN) and ear is augmented during TDI sensitization. In order to further investigate the functional role of miR-210 and Tregs during TDI sensitization, BALBc mice were dermally exposed to a single, sensitizing dose of TDI (0.5-4% v/v) and evaluated for immunological endpoints. Alterations in expression of putative miR-210 transcription factor targets were observed in the dLN during TDI sensitization. These transcription factors are directly involved in Treg expansion and function; therefore, miR-210 may potentially negatively target Treg differentiation and function during TDI sensitization. dLN Tregs were phenotyped during TDI sensitization and a heterogeneous population was observed. To examine Treg functionality, a carboxyfluorescein succinimidyl ester-based Treg suppression assay was conducted. Tregs isolated from the dLNs of TDI sensitized mice were more suppressive than their control counterparts. The Treg population was then depleted prior to TDI sensitization by in vivo administration of a CD25-targeting antibody. The sensitization response was intensified following Treg depletion, as evidenced by amplified total dLN cellularity, Th2 expansion, and IL-4 mRNA production. These novel findings indicate that Tregs may play an important role in modulating allergic responses during TDI sensitization and that miR-210 may have an inhibitory role in this process. These data are necessary to fully understand the immunologic mechanisms of chemical-induced allergic disease and may aid in the development of preventative and therapeutic strategies. [Description provided by NIOSH]
• Subjects:
  Antibodies Biological Assay Esters Hypersensitivity Immune System Laboratories Occupational Health Safety Toluene Toxicology
• Keywords:
  Allergic Reactions Bioassays Chemical Agents Chemical Inhibition Exposure Assessment Gene Expression Gene Regulation Immune System Immunological Tests Laboratory Animals Models Ribonucleic Acids RNA Sensitization Sensitizers Toluene-2,4-diisocyanate

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047725
• Citation:
  Toxicologist 2016 Mar; 150(1):437
• CAS Registry Number:
  Toluene diisocyanate (CAS RN 26471-62-5)
• Federal Fiscal Year:
  2016
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 55th Annual Meeting and ToxExpo, March 13-17, 2016, New Orleans, Louisiana
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:64163e2237f4368038b37d1f9700a83e5b784df0d09fddd4c48067eebe9719d264e3a1e4bc206e8ca704246ab341832da4f14665333c9c33fb82feb9981c6eef
• Download URL:
  https://stacks.cdc.gov/view/cdc/202722/cdc_202722_DS1.pdf
• File Type:
  [PDF - 443.17 KB ]