Mir-363-5p Modulates Regulatory T Cells Through Stat4-Hspb1-Notch1 Axis And Is Associated With The Immunological Abnormality In Graves' Disease

MiRNAs are a class of small non-coding RNAs with ability to regulate function of Treg cells and are involved in many autoimmune diseases. Our previous study found that miR-363-5p expression was significantly upregulated in peripheral Treg cells of GD patients. Herein, we aimed to investigate its effect and mechanism on Treg cell dysfunction in GD patients. The results showed that miR-363-5p upregulation was significantly associated with the Treg cell dysfunction and inflammatory factors levels in GD patients. Transcriptome sequencing revealed that 883 genes were significantly regulated by miR-363-5p in Treg cells. These genes with significant differential expression were primarily involved in lymphocyte differentiation, immunity, as well as Notch1 and various interleukin signalling pathways. Moreover, miR-363-5p can regulate HSPB1 and Notch1 through the target gene STAT4, thereby regulating Notch1 signalling pathway and inhibiting Treg cells. The effects of miR-363-5p on Treg cell function and STAT4-HSPB1-Notch1 axis were also verified in GD patients. In conclusion, our results indicated that miR-363 could inhibit the proliferation, differentiation and function of Treg cells by regulating the STAT4-HSPB1-Notch1 axis through target gene STAT4. MiR-363-5p may play an important role in Treg cell dysfunction and immune tolerance abnormalities in GD patients.