Comprehensive Analysis of the miRNA-mRNA Pathological Regulatory Network of Intestinal CD4 + T Cells in Parkinson's Disease.

Abstract

Infiltration of CD4 + T cells was found in brain tissue samples from PD patients, suggesting their involvement in developing central nervous system (CNS) disease. The idea of the gut-brain axis further corroborates intestinal T cells' activation as the central immune response initiation. However, the specific factors and molecular pathways regulating intestinal T-cell activation are unclear. We used the GSE156287 and GSE145814 datasets from the GEO database to analyze and obtain the miRNAs, which are aberrantly expressed in intestinal CD4 + T cells in PD patients and predict their regulatory target mRNAs. Further, combined with the GSE174473 dataset of CD4 + T cells sequencing in PD patients, we finally clarified the aberrant genes expressed in CD4 + T cells from the intestine of PD patients and constructed a miRNA-mRNA regulatory network. The highlight of our findings showed pathways, networks, biological functions, and key molecules potentially involved in the miRNA-mediated functional effects in CD4 + T cell from the intestine of PD patients. The hsa-miR-3180-3p mediated CBX8, etc. were determined as most effective in enhancing T cell survival. PEG10, etc. regulated by hsa-miR-20a-3p targets were possibly involved in T cell differentiation. The JPT2 regulated by hsa-miR-1281 were involved in influencing T cell infiltration. The discovery of this interaction between miRNA and mRNA in CD4 + T cell has important implications for understanding the intestinal initial of PD pathological molecular and anti-inflammation of T cell activation.