MiR-346 regulates CD4⁺CXCR5⁺ T cells in the pathogenesis of Graves' disease

Follicular helper T (Tfh) cells are increasingly recognized as participants in various autoimmune diseases, including Graves' disease. Although many transcription factors and cytokines are known to regulate Tfh cells, the role of noncoding RNA in Tfh cells development and function is poorly understood. Twenty-three patients with GD, eleven patients with remitting GD, and twenty-four healthy controls were enrolled in the current study. The interaction of miRNA and target gene was predicted through software analysis and then validated by luciferase assay and Western blot. The levels of miR-346 in circulating CD4(+) T cells and plasma were measured by qRT-PCR. The correlation of miR-346 levels with the percentages of CD4(+)CXCR5(+)T cells and autoantibody levels were also analyzed. Up-regulation of Bcl-6 and down-regulation of miR-346 in GD patients were observed, and miR-346 could inhibit Bcl-6 at both transcriptional and translational levels. Overexpression of miR-346 led to attenuating CD4(+)CXCR5(+) T cells. The abnormal expression of miR-346 restored in GD patients after treatment. A negative correlation between levels of miR-346 and percentages of CD4(+)CXCR5(+) T cells was confirmed in GD patients. Additionally, negative correlations between the levels of miR-346 in circulating CD4(+) T cells and serum concentrations of TR-Ab, TG-Ab, and TPO-Ab were also revealed in GD patients. MiR-346 regulates CD4(+)CXCR5(+) T cells by targeting Bcl-6, a positive regulator of Tfh cells, and might play an important role in the pathogenesis of Graves' disease.