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

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(+)CXCR5(hi)PD-1(hi)cTfh, CD4(+)CXCR5(hi)PD-1(hi)ICOS(hi), and CD4(+)CXCR5(hi)PD-1(hi)Bcl-6(+) populations were significantly increased in SLE patients (n=70) when compared with healthy controls (n=48). Surprisingly, only CD4(+)CXCR5(hi)PD-1(hi)Bcl-6(+) cTfh cells, rather than CD4(+)CXCR5(hi)PD-1(hi) 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.