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

Details

• Alternative Title:
  Front Neurosci
• Personal Author:
  Gao, Jun ; Xu, Fuyi ; Starlard-Davenport, Athena ; Miller, Diane B. ; O’Callaghan, James P. ; Jones, Byron C. ; Lu, Lu
• 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 | 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 | as a candidate gene underlying individual differences in susceptibility to GWI. The | gene is |-regulated and its expression is significantly correlated with CORT+DFP treatment. Its mean transcript abundance in PFC of BXD mice decreased 1.6-fold (| < 0.0001) in the CORT+DFP group. The response of | to CORT+DFP is also significantly different (| < 0.0001) between the parental strains, suggesting | is affected by both host genetic background and chemical treatments. Pearson product-moment correlation analysis revealed 1473 |-correlated genes (| < 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 (| < 0.05) with expression of | in the PFC. We further established a protein-protein interaction subnetwork for the |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 | is one of promising GWI biomarkers.
• Subjects:
  BXD Strain Ccr6 CORT DFP GWI Neuroinflammation Neuroscience RNA-seq
• Source:
  Front Neurosci. 2020; 14
• Pubmed ID:
  32922257
• Pubmed Central ID:
  PMC7456958
• Document Type:
  Journal Article
• Volume:
  14
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:a50e4fe463ac2a45b59e7289c54b603b609229f92a15adfd9f4ff411e7c3ab39
• Download URL:
  https://stacks.cdc.gov/view/cdc/97247/cdc_97247_DS1.pdf
• File Type:
  [PDF - 7.07 MB ]