Relationship Between FOXP3 Positive Populations and Cytokine Production in Systemic Lupus Erythematosus

Cytokine. 2013 Jan;61(1):90-6. doi: 10.1016/j.cyto.2012.08.033. Epub 2012 Sep 28.

Abstract

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. CD25low 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 CD25highFOXP3+ 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, CD25high cells showed an altered balance in the production of these cytokines. In addition, CD25highFOXP3+ cells correlated directly with IL-17A and IL-8 but not with TGFβ in SLE. The increased proportion of IL-17+ cells among the CD25high subset and the positive correlation between IL-17 levels and Treg cells suggest a trans-differentiation of Treg into Th17 cells in SLE.

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Transdifferentiation
  • Cytokines / metabolism*
  • Disease Progression
  • Down-Regulation
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Interleukin-17 / metabolism*
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lupus Erythematosus, Systemic* / blood
  • Lupus Erythematosus, Systemic* / immunology
  • Lupus Erythematosus, Systemic* / metabolism
  • Male
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Up-Regulation

Substances

  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • Interleukin-2 Receptor alpha Subunit