Objectives <p>The imbalance of Th17 cells and Treg cells in synovium participates in rheumatoid arthritis (RA), and lycium barbarum polysaccharide (LBP) can attenuate arthritis in mice. The study aimed to explore the causes of Th17/Treg cell imbalance and investigate whether LBP could correct this imbalance in patients with RA.</p> Methods <p>The study recruited 23 healthy controls and 58 RA patients. Flow cytometry was used to analyze the percentage of C–C chemokine receptor 9⁺ (CCR9) Th17 cells and CCR9⁺ Treg cells. IL-17A and IL-10 were evaluated by enzyme-linked immunosorbent assay. LBP was added to Treg cells or Th17 cells differentiation system to explore the role of LBP in differentiation of CCR9⁺ Th17/Treg cells.</p> Results <p>In the peripheral blood (PB) and synovial fluid (SF) of RA patients, there was a rise in the proportion of CCR9⁺ Th17 cells and a decline in the proportion of CCR9⁺ Treg cells. Furthermore, a positive association was observed between the CCR9⁺ Th17/Treg ratio in PB and disease activity. In vitro, LBP could promote the differentiation of CCR9⁺ Treg cells and inhibit the differentiation of CCR9⁺ Th17 cells.</p> Conclusions <p>In summary, the CCR9⁺ Th17/ Treg ratio is increased in peripheral blood and synovial fluid in patients with RA, and LBP can correct the CCR9⁺ Th17/ Treg cells imbalance.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> <p><b>Key Points</b></p> <p>• <i>CCR9+ Th17/ Treg ratio is increased in PB and SF in patients with RA.</i></p> <p>• <i>LBP can correct the CCR9+ Th17/ Treg cells imbalance in vitro.</i></p> </entry> </row> </tbody> </tgroup> </Table></p>