Positive correlation of increased serum IL-21 with circulating T follicular helper (Tfh)-like cells in patients with rheumatoid arthritis (RA). (a) Serum IL-21 positively correlated with the percentages of circulating Tfh-like cells in RA patients with high IL-21 (n = 16). (b) IL-21 derived from both CXCR5+CD4+ T cells and CXCR5-CD4+ T cells in RA patients (n = 20). (c) IL-21R expression on Tfh-like cells in peripheral blood (PB) from RA patients (n = 47) was substantially upregulated compared to healthy controls (HC) (n = 34). (d) IL-21R expression on CXCR5-CD4+T cells was unchanged in RA patients. (e) IL-21 had no relationship with IL-21R expression on Tfh-like cells in RA patients with high IL-21 (n = 16). (f) Peripheral blood mononuclear cells (PBMC) isolated from either RA patients (n = 8) or HC (n = 8) were cultured with 10 μg/ml phytohemagglutinin (PHA; Sigma) in the presence and absence of rIL-21 (100 ng/ml), and IL-21R expression on Tfh-like cells was analyzed after 48 h.*P < 0.05; n.s., not significant. PBS, phosphate-buffered saline.