Relationship between FOXP3 positive populations and cytokine production in systemic lupus erythematosus

In this work we studied CD4(+)FOXP3(+) populations in systemic lupus erythematosus (SLE) and the relationship with Th cytokine production. We found an increment in CD25(-)FOXP3(+). population in SLE associated with CD4(+) downregulation and disease progression. CD25(low) cells were also upregulated and showed increased percentages of FOXP3(+) and CD127(-/low) cells, supporting the activated status of SLE lymphocytes. Despite the normal levels of CD25(high)FOXP3(+) cells, the negative correlations observed in controls with the frequency of IFN gamma, TNF alpha and IL-10 secreting cells were disrupted in patients, supporting a defective Treg function. Also, CD25(high) cells showed an altered balance in the production of these cytokines. In addition, CD25(high)FOXP3(+) cells correlated directly with IL-17A and IL-8 but not with TGF beta in SLE. The increased proportion of IL-17(+) cells among the CD25(high) subset and the positive correlation between IL-17 levels and Treg cells suggest a trans-differentiation of Treg into Th17 cells in SLE. (C) 2012 Elsevier Ltd. All rights reserved.