Dysregulated T Cell Activation and Aberrant Cytokine Expression Profile in Systemic Lupus Erythematosus

Mediators Inflamm. 2019 Mar 17:2019:8450947. doi: 10.1155/2019/8450947. eCollection 2019.

Abstract

Accumulating evidence indicates a critical role for T cells and relevant cytokines in the pathogenesis of systemic lupus erythematosus (SLE). However, the specific contribution of T cells together with the related circulating cytokines in disease pathogenesis and organ involvement is still not clear. In the current study, we investigated relevant molecule expressions and cytokine levels in blood samples from 49 SLE patients and 22 healthy control subjects. The expression of HLA-DR and costimulatory molecules on T cells was evaluated by flow cytometry. Concentrations of serum C-reactive protein, erythrocyte sedimentation rate, anti-double-stranded DNA (anti-dsDNA) antibody, total lgG, complement 3, and complement 4 were measured. Serum cytokines and chemokines were measured by a cytometric bead array assay. Elevated frequencies of HLA-DR+ T cells and ICOS+ T cells were observed in SLE patients with positive anti-dsDNA antibodies compared with those in healthy controls (P < 0.001). The expression of HLA-DR+ T cells was positively correlated with SLEDAI (r = 0.15, P < 0.01). Furthermore, levels of serum IL-6, MCP-1, TNFRI, IL-10, IL-12, and CCL20 were higher in SLE patients compared with healthy controls. In addition, patients with hematologic manifestations displayed elevated frequencies of HLA-DR+ T cells and ICOS+ T cells. Patients with renal manifestations had a decreased frequency of TIGIT+ T cells. These results suggested a dysregulated T cell activity and cytokine expression profiles in SLE subjects. We also developed a chemokine and cytokine profiling strategy to predict the activity of SLE, which has clinical implication for better monitoring the flares and remission during the course of SLE and for assessing therapeutic interventions.

MeSH terms

  • Adult
  • Aged
  • C-Reactive Protein / metabolism
  • Chemokine CCL17 / blood
  • Chemokine CCL20 / blood
  • Complement C3 / metabolism
  • Complement C4 / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin G / blood
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / metabolism
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Chemokine CCL17
  • Chemokine CCL20
  • Complement C3
  • Complement C4
  • Immunoglobulin G
  • C-Reactive Protein