Immunoregulation therapy changes the frequency of interleukin (IL)-22+ CD4+ T cells in systemic lupus erythematosus patients

Clin Exp Immunol. 2014 Jul;177(1):212-8. doi: 10.1111/cei.12330.

Abstract

T cell and T cell-related cytokine abnormalities are involved in the pathogenesis of systemic lupus erythematosus (SLE). Our previous study showed that the interleukin (IL)-22(+) CD4(+) T cells and IL-22 play an important role in the pathogenesis of SLE. In this study, we aimed to investigate the effects of glucocorticoids (GCs) and immunodepressant agents on IL-22 and IL-22-producing T cell subsets in SLE patients. The frequencies of peripheral blood T helper type 22 (Th22), IL-22(+) Th17, IL-22(+) Th1 and Th17 cells and the concentrations of serum IL-22, IL-17 and interferon (IFN)-γ in SLE patients receiving 4 weeks of treatment with cyclophosphamide (CYC), methylprednisolone and hydroxychloroquine (HCQ) were characterized by flow cytometry analysis and enzyme-linked immunosorbent assay (ELISA). The frequencies of Th22, IL-22(+) Th17 and Th17 cells and the concentrations of IL-22 and IL-17 were reduced in response to the drugs methylprednisolone, cyclophosphamide and hydroxychloroquine for 4 weeks in the majority of SLE patients. However, the percentage of Th1 cells showed no change. No differences in the levels of IL-22 and IL-22(+) CD4(+) T cells were found between non-responders and health controls either before or after therapy. IL-22 levels were correlated positively with Th22 cells in SLE patients after treatment. These results suggest that elevated IL-22 is correlated with IL-22(+) CD4(+) T cells, especially Th22 cells, and may have a co-operative or synergetic function in the immunopathogenesis of SLE. GC, CYC and HCQ treatment may regulate the production of IL-22, possibly by correcting the IL-22(+) CD4(+) T cells polarizations in SLE, thus providing new insights into the mechanism of GC, CYC and HCQ in the treatment of SLE.

Keywords: IL-22; Th22; cyclophosphamide; systemic lupus erythematosus.

MeSH terms

  • Adolescent
  • Adult
  • CD4 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / drug effects
  • Cell Lineage / drug effects
  • Cyclophosphamide / administration & dosage
  • Female
  • Homeostasis
  • Humans
  • Hydroxychloroquine / administration & dosage
  • Immunomodulation
  • Immunosuppressive Agents / administration & dosage
  • Immunotherapy / methods*
  • Interferon-gamma / blood
  • Interleukin-22
  • Interleukins / immunology
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / therapy*
  • Male
  • Methylprednisolone / administration & dosage
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Young Adult

Substances

  • CD4 Antigens
  • Immunosuppressive Agents
  • Interleukins
  • Hydroxychloroquine
  • Interferon-gamma
  • Cyclophosphamide
  • Methylprednisolone