Modulation of STAT3 and STAT5 activity rectifies the imbalance of Th17 and Treg cells in patients with acute coronary syndrome

- Up-regulation of STAT3 and down-regulation of STAT5 activities was found in ACS patients.
- Imbalance of STAT3 and STAT5 activity leads to expansion of Th17 but reduction of Treg cells.
- Specific knockdown of STAT3 could rectify the imbalance of Th17/Treg cells in ACS patients.
- STAT3 knockdown leads to more STAT5 binding to Foxp3 locus in ACS patients.
- Overexpression of STAT5 in CD4+ T cells in ACS increased Treg cells and decreased Th17 cells.

The signal transducer and activator of transcription (STAT) activity plays an important role in the differentiation and imbalance of Th17 and Treg cells in acute coronary syndrome (ACS) patients. We determined that the basal STAT3 phosphorylation level was significantly increased and exhibited a positive relationship with Th17 cells but was negatively correlated with Treg cells in ACS patients. Opposite effects were observed for STAT5 activity. Using the pharmaceutical inhibitor TG101348 or knockdown of STAT3 reduced the number of Th17 cells while promoting the number and function of Treg cells via the Janus kinase2 (JAK2)/STAT3 pathway in ACS patients. Significantly more STAT5 bound to the Foxp3 locus when STAT3 was knocked down, and overexpression of STAT5 led to an increased number of Treg cells but a decreased number of Th17 cells in ACS patients. Our findings demonstrate that modulation of STAT3/STAT5 activity rectifies the imbalance of Th17/Treg cells in ACS patients.