Interleukin 21 Correlates with T Cell and B Cell Subset Alterations in Systemic Lupus Erythematosus

Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by alterations of the B cell subset, global regulatory T cell (Treg) depletion, and an increase in Th17 cells. Interleukin 21 (IL-21) plays a critical role in T cell and B cell homeostasis. Our objective was to determine the implication of IL-21 and IL-21-producing CD4+ T cells in the pathogenesis of SLE. Methods. Twenty-five patients with SLE and 25 healthy donor controls were included. Analysis of CD4+ T cells producing IL-21, Th1, Th2, Th17, Treg, follicular helper T (TFH) cells, and B cells was performed in peripheral blood, and levels of cytokines were measured in culture supernatants. Results. Circulating CD4+ T cells producing 1L-21 were markedly expanded in patients with SLE compared to controls and were correlated with increased Th17, decreased Treg, and increased memory B cells. CD4+ T cells producing IL-21 were composed of CXCR5+ and CXCR5 CD4+ T cell subsets. Both IL-21-producing CXCR5+CD4+ T cells and CXCR5 CD4+ T cells were increased in patients with SLE, the CXCR5 CD4+ subset correlating with Th17 cells and Treg, while the CXCR5+CD4+ subset was correlated with alterations of the B cell subset. The CXCR5+CD4+ subset comprised mainly circulating Bc16+CXCR5+CD4+ TFH cells that were markedly expanded in patients with SLE and were correlated with increased circulating Bc16+CXCR5+ germinal center B cells. Conclusion. These findings suggest that IL-21, produced by distinct cellular CD4+ T cells, correlates with alterations of T cell and B cell subsets in SLE, and that targeting IL-21 could provide beneficial effects on both T cell and B cell alterations. (First Release Aug 1 2012; J Rheumatol 2012;39:1819-28; doi:10.3899/jrheum.120468)