Significance of increased IL-17-producing Foxp3+ Treg in peripheral blood of patients with active systemic lupus erythematosus
Objective 
To investigate the expression of IL-17-producing regulatory T cells (Treg) in patients with systemic lupus erythematosus (SLE) and to analyze their clinical significance. 
 
 
Methods 
This study recruited 32 patients with SLE (including 14 with active SLE and 18 with inactive SLE) and 13 healthy subjects matched for age and sex. Flow cytometry was performed to detect the expression of Foxp3 and IL-17 in CD4 T lymphocytes and the phenotypic characteristics of IL-17-producing Treg. Correlations between these cells and clinical indicators of SLE were analyzed. Peripheral CD4+ CD25+ T cells were isolated from five healthy subjects and then stimulated with IL-6 and IL-1β alone or in combination. An in vitro T cell polarization assay was performed to investigate the role of cytokines in the polarization and regulation of IL-17-producing Treg. 
 
 
Results 
Compared with the healthy subjects and patients with inactive SLE, the patients with active SLE had a higher percentage of IL-17-producing Treg in peripheral blood. Moreover, the expression of Foxp3 and CD45RA by IL-17-producing Treg in the active SLE group was down-regulated, while that of IL-2, granzyme B (GramB), programmed cell death protein 1 (PD-1) and glucocorticoid-induced tumor necrosis factor receptor (GITR) was up-regulated. Inflammatory cytokines such as IL-6 and IL-1 could induce Treg to produce IL-17. 
 
 
Conclusions 
This study suggested that increased inflammatory cytokines might correlate with higher percentages of IL-17-producing Treg in patients with active SLE. These cells were a subset of pathogenic Treg failing to prevent autoimmune. 
 
 
Key words: 
Regulatory T cell; Interleukin-17; Inflammatory cytokine; Immunophenotype; T cell plasticity