Exploring the Role of Chemokine Receptor 6 (Ccr6) in the BXD Mouse Model of Gulf War Illness

Details

• Personal Author:
  Gao J ; Jones BC ; Lu L ; Miller DB ; O'Callaghan JP ; Starlard-Davenport A ; Xu F
• Description:
  Gulf War illness (GWI) is a chronic and multi-symptomatic disorder with persistent neuroimmune symptomatology. Chemokine receptor 6 (CCR6) has been shown to be involved in several inflammation disorders in humans. However, the causative relationship between CCR6 and neuroinflammation in GWI has not yet been investigated. By using RNA-seq data of prefrontal cortex (PFC) from 31 C57BL/6J X DBA/2J (BXD) recombinant inbred (RI) mouse strains and their parental strains under three chemical treatment groups - saline control (CTL), diisopropylfluorophosphate (DFP), and corticosterone combined with diisopropylfluorophosphate (CORT+DFP), we identified Ccr6 as a candidate gene underlying individual differences in susceptibility to GWI. The Ccr6 gene is cis-regulated and its expression is significantly correlated with CORT+DFP treatment. Its mean transcript abundance in PFC of BXD mice decreased 1.6-fold (p < 0.0001) in the CORT+DFP group. The response of Ccr6 to CORT+DFP is also significantly different (p < 0.0001) between the parental strains, suggesting Ccr6 is affected by both host genetic background and chemical treatments. Pearson product-moment correlation analysis revealed 1473 Ccr6-correlated genes (p < 0.05). Enrichment of these genes was seen in the immune, inflammation, cytokine, and neurological related categories. In addition, we also found five central nervous system-related phenotypes and fecal corticosterone concentration have significant correlation (p < 0.05) with expression of Ccr6 in the PFC. We further established a protein-protein interaction subnetwork for the Ccr6-correlated genes, which provides an insight on the interaction of G protein-coupled receptors, kallikrein-kinin system and neuroactive ligand-receptors. This analysis likely defines the heterogeneity and complexity of GWI. Therefore, our results suggest that Ccr6 is one of promising GWI biomarkers. [Description provided by NIOSH]
• Subjects:
  Chronic Disease Genetics Immune System Laboratories Nervous System Occupational Health Safety
• Keywords:
  Analytical Models Author Keywords: Ccr6 Biological Weapons Brain Matter BXD Strain Chemical Warfare Agents Chronic Diseases CORT Corticosteroids DFP Diseases Gene Regulation Genes GWI Immune Reaction Immune System Immune System Disorders Laboratory Animals Military Personnel Neuroinflammation Neurological Diseases Neurotoxic Effects Proteins Ribonucleic Acids RNA RNA-seq

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• ISSN:
  1662-4548
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; OSHA Region 4 ; Tennessee ; 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:
  14
• NIOSHTIC Number:
  nn:20060835
• Citation:
  Front Neurosci 2020 Aug; 14:818
• Contact Point Address:
  Lu Lu, Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN, United States
• Email:
  llu@uthsc.edu
• CAS Registry Number:
  Diisopropyl fluorophosphate (CAS RN 55-91-4)
• Federal Fiscal Year:
  2020
• Peer Reviewed:
  True
• Source Full Name:
  Frontiers in Neuroscience
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7ba3d558c6fcb32613e7edf95b7eeff2f34517aebd3c127944de8f4a71d95e45246cf5dafa34889a8422ffb7cc72fe6938aabe98c117b596a297911ed2e64878
• Download URL:
  https://stacks.cdc.gov/view/cdc/224632/cdc_224632_DS1.pdf
• File Type:
  [PDF - 6.97 MB ]