The expression of Bcl-6 in circulating follicular helper-like T cells positively correlates with the disease activity in systemic lupus erythematosus

- The expression of Bcl-6 in CD4+ CXCR5hiPD-1hi cTfh cells is increased in SLE patients and correlated with disease activity.
- The frequency of CD4+ CXCR5hiPD-1hiBcl-6+ cells in peripheral blood of SLE is positively associated with anti-dsDNA Abs.
- An increased level of IL-21 has been found in SLE patients and IL-21 might be a key player that increases Bcl-6 expression.

Increased circulating follicular helper-like T cells (cTfh) are reported in systemic lupus erythematosus (SLE) patients. However, whether B-cell lymphoma 6 (Bcl-6) is expressed in cTfh cells remains to be clarified. In this study, we found that the frequencies of CD4+ CXCR5hiPD-1hicTfh, CD4+ CXCR5hiPD-1hiICOShi, and CD4+ CXCR5hiPD-1hiBcl-6+ populations were significantly increased in SLE patients (n = 70) when compared with healthy controls (n = 48). Surprisingly, only CD4+ CXCR5hiPD-1hiBcl-6+ cTfh cells, rather than CD4+ CXCR5hiPD-1hi population, were positively correlated with SLEDAI and anti-dsDNA antibodies. An elevated level of IL-21 was found in SLE CD4+ T cells. Moreover, IL-21 promoted the enrichment of TET2 in Bcl-6 promoter region and induced Bcl-6 expression. Therefore, Bcl-6 expression in cTfh cells may represent a reliable marker for the disease activity in SLE.