miR-181a regulates Th17 cells distribution via up-regulated BCL-2 in primary biliary cholangitis

Abstract

Background: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterised by destruction of small intrahepatic bile ducts. Recent studies suggest that miRNAs play a critical role in the pathogenesis of liver diseases. However the role served by miRNAs in the pathogenesis of PBC is still not clear.

Methods: The differentially expressed genes and miRNAs were identified by bioinformatics analysis. Gene ontology and KEGG pathway analyses were conducted to explore the function of the differentially expressed genes. miRNA target genes were predicted using miRecords. The differentially expressed genes and miRNAs were validated by qRT-PCR in PBC patients along with healthy controls and chronic hepatitis B patients as control. Flow cytometric analysis was conducted to identify the Th17 and Treg cells frequency.

Results: 15 differentially expressed miRNAs and 1897 mRNAs were identified from the profile. miR-181a was validated as the differentially expressed miRNA. BCL-2 and CDKN1B were predicted as the target gene of miR-181a and validated differentially expressed in PBC patients. However, only BCL-2 was negative correlated with miR-181a. The Th17 cells frequency was increased in PBC patients while the Treg cells frequency was decreased. Moreover, the expression of BCL-2 was positive correlated with Th17 cells frequency.

Conclusion: Down-regulated miR-181a in CD4+ T cells may decrease apoptosis of Th17 cells via up-regulated BCL-2 in the pathogenesis of PBC.

Keywords: Autoimmune disease; BCL-2; CDKN1B; Primary biliary cholangitis; miR-181a.