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^highFOXP3⁺ cells, the negative correlations observed in controls with the frequency of IFNγ, TNFα 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^highFOXP3⁺ cells correlated directly with IL-17A and IL-8 but not with TGFβ 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.