IL-6 alters migration capacity of CD4+Foxp3+ regulatory T cells in systemic lupus erythematosus.

Abstract

Regulatory T cells (Tregs) are impaired in human systemic lupus erythematosus (SLE) and involved in disease pathogenesis. However, the mechanisms responsible for the Treg dysfunction in SLE remain unclear. In this study, we aimed to investigate the chemotaxis of Treg response to inflammatory stimulation. Sixty two patients were enrolled, and chemokine receptors, including CCR4, CCR5, CCR6, CCR8 and CXCR3 on CD4+Foxp3+Tregs and non-Treg CD4 T cells, were analysed using FACS. The expression of CCR4 and CCR6 on Tregs of SLE patients decreased, while the expression of CCR4 on non-Treg CD4 T cells increased, as compared with those of age- and sex-matched healthy donors. In parallel, in SLE, the chemotactic capacity of non-Treg CD4 T cells response to CCR4 and CCR6 ligands dramatically increased, while that of Tregs significantly decreased. Moreover, we found that cytokines IL-6 and IL-10 positively and negatively modulate the expression of those receptors respectively. IL-6, the significantly increased cytokine in active SLE, dramatically elevated CCR4 and CCR6 expression on non-Treg CD4 T cells. However, as for Tregs, these cells produced more IL-10 than non-Treg CD4 T cells upon IL-6 stimulation, and these IL-10 led to the inhibition of CCR4 and CCR6. In sum, our data provided new evidence suggesting a functional deficiency of Tregs in SLE. It may suggest that those dysfunctional Tregs have less access to the inflammation locus to exert inhibitory capacity.