Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus

Arthritis Res Ther. 2010;12(2):R53. doi: 10.1186/ar2964. Epub 2010 Mar 24.


Introduction: Interleukin (IL)-17 is a proinflammatory cytokine that is produced largely by a unique CD4(+) T-helper (Th) subset called Th17 cells. The development of Th17 cells is suppressed by interferon (IFN)-gamma produced by Th1 cells, suggesting cross-regulation between Th17 and Th1 cells. Thus, this study analyzed the balance of CD4+ Th17 and Th1 cell responses in peripheral blood from patients with systemic lupus erythematosus (SLE) and healthy subjects.

Methods: Twenty-five adult patients with SLE and 26 healthy subjects matched for gender and age (+/- 2 years) were recruited. Peripheral blood mononuclear cells (PBMCs) from patients and healthy subjects were stimulated for 4 h ex vivo with phorbol myristate acetate (PMA) and ionomycin. The frequency of CD4(+) T cells producing IL-17 and/or IFN-gamma was measured by using flow cytometry. Expression of Th17-associated chemokine receptors CCR4 and CCR6 on CD4(+) T cells as well as plasma levels of Th17-polarizing cytokines were assessed. Disease activity was evaluated by the SLE disease activity index score (SLEDAI). Unpaired t test and Pearson correlation were used for statistical analyses.

Results: Patients with SLE had an increased frequency of CD4(+)IL-17(+) T cells compared with healthy subjects. However, the frequency of CD4(+)IFN-gamma(+) T cells was similar between the two groups, indicating an altered balance of Th17 and Th1 cell responses in SLE. Patients with SLE also had an increased frequency of CD4(+)CCR4(+)CCR6(+) T cells that are known to produce IL-17. The frequency of CD4(+)IL-17(+) T cells and CD4(+)CCR4(+)CCR6+ T cells correlated with disease activity. In measuring plasma levels of the Th17-polarizing cytokines, levels of IL-6 were higher in patients with SLE than in healthy subjects, although levels of IL-1beta, IL-21, IL-23, and transforming growth factor (TGF)-beta were not different between the two groups.

Conclusions: We demonstrate an enhanced Th17 cell response that correlates with disease activity in patients with SLE, suggesting a role for IL-17 in the pathogenesis of lupus. Our data indicate that the mechanisms involved in balancing Th1 and Th17 regulation, as well as in producing IL-6, are aberrant in SLE, leading to an increased Th17 response. We suggest that CCR4 and CCR6 expression on CD4(+) T cells should be considered as markers of disease activity, and that IL-17 blocking may offer a therapeutic target in SLE.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Female
  • Health Status
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Interleukin-17 / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / physiopathology
  • Lymphocyte Activation
  • Male
  • Receptors, CCR4 / metabolism
  • Receptors, CCR6 / metabolism
  • Severity of Illness Index
  • Th1 Cells / immunology*


  • CCR4 protein, human
  • CCR6 protein, human
  • Immunosuppressive Agents
  • Interleukin-17
  • Receptors, CCR4
  • Receptors, CCR6