MicroRNA-21-5p participates in IgA nephropathy by driving T helper cell polarization

Previous studies have revealed abnormal lymphocyte subsets in IgA nephropathy (IgAN). Some microRNAs have been reported to influence T helper differentiation. Here, we explored the underlying mechanism regarding how miRNAs regulate lymphocyte subsets in IgAN.

First, miRNA and mRNA profiles in PBMCs from IgAN patients and controls were obtained by next-generation sequencing and gene expression array. The target miRNAs and mRNAs were identified through combined analysis. Then, in an independent population, we detected the expression of target miRNA in CD3⁺ T cells and CD19⁺ B cells. Next, we detected T helper cell subgroups and plasma IgA1 levels in another independent population and analyzed the correlations between them.

In total, 22 differentially expressed miRNAs were identified between IgAN patients and controls. Among them, microRNA-21-5p (miR-21) showed the highest expression, and SPRY1, SPRY2, and FASLG were chosen as miR-21 target genes. Then, we confirmed elevated miR-21 levels in CD3⁺ T cells of IgAN patients. Accordingly, decreased mRNA levels of SPRY1, SPRY2, and FASLG were found, and miR-21 showed a significant negative correlation with SPRY1 levels in CD3⁺ T cells of IgAN patients. Finally, we revealed that the proportion of Th17 cells was significantly elevated in IgAN patients and negatively correlated with SPRY1 expression. Furthermore, the proportion of Th17 cells showed a positive correlation trend with plasma IgA1 levels.

Our results suggested that in IgAN, the upregulated miR-21 expression in T lymphocytes inhibited SPRY1 expression and thereby induced Th17 polarization, which might influence the characteristic feature of IgA1 overproduction in IgAN patients.