The shifted balance between circulating follicular regulatory T cells and follicular helper T cells in patients with ulcerative colitis

B-cell immunity participates in the pathogenesis of ulcerative colitis (UC). The immune balance between follicular regulatory T (TFR) cells and follicular helper T (TFH) cells is important in regulating B-cell responses. However, the alteration of TFR/TFH balance in UC remains unclear. Peripheral blood from 25 UC patients and 15 healthy controls was examined for the frequencies of circulating TFR, TFH, and regulatory T (Treg) cells by flow cytometry. Levels of serum cytokines were measured using cytometric bead array (CBA). Disease activity was evaluated by the Mayo Clinic Score. Compared with controls, UC patients exhibited significant reductions in circulating Foxp3⁺CXCR5⁺ TFR cells, the subset interleukin (IL)-10⁺Foxp3⁺CXCR5⁺ cells, and Treg cells, but significant expansions in Foxp3⁻CXCR5⁺ TFH cells and IL-21⁺Foxp3⁻CXCR5⁺ cells. UC patients also had reduced levels of serum IL-10 and elevated levels of serum IL-21. The values of Mayo Clinic Score, C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) in UC patients were negatively correlated with circulating TFR cells, serum IL-10 level, and TFR/TFH ratio, while positively correlated with circulating TFH cells and serum IL-21 level. Alterations in circulating TFR and TFH cells shift the balance from immune tolerance to immune responsive state, contributing to dysregulated B-cell immunity and the pathogenesis of UC.