Front Neurosci

Abstract

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.32922257PMC7456958867