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THU0226 Differential susceptibility of TH17 and T regulatory cells to apoptosis in systemic lupus erythematosus patients – the modulatory effects of statin
  1. J Sun,
  2. J Frostegard,
  3. A Liu
  1. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Abstract

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder. Patients with SLE have accelerated cardiovascular disease. Recent studies show there are more Th17 while less T regulatory (Treg) cells in the SLE patients. Th17/Treg imbalance may contribute to the pathogenesis of SLE.

Objectives To investigate the underlying mechanisms of Th17/Treg imbalance, we test the proportion and susceptibility of Th17 and Treg to apoptosis, and the modulatory effects of statin in the SLE patients.

Methods Totally 17 SLE patients and 20 gender- and age-matched control subjects were enrolled for this study. Peripheral blood mononuclear cells were isolated, either analyzed ex vivo, or cultured in the conditions to induce Th17 and/or Treg polarization. The proportion of Th17/Treg cells and frequency responding to apoptosis were analyzed by multiple color flow cytometry. Cytokines in cell culture supernatants and plasma were tested by ELISA. T cell polarization-related transcription factors were detected by quantitative real time PCR.

Results The proportion of Th17 (CD4+IL17+) cells were higher in SLE patients, both in ex vivo and in the Th17-polarizing cultures. While the frequencies of Treg (CD4+CD25+CD127dim/-) cells were lower in the corresponding populations. Higher levels of IL17 and IL6 were detected in plasma of SLE patients. Responding to CD95-induced apoptosis the frequency of CD4+IL17+ cells from SLE patients was substantially lower, but that of CD4+CD25+CD127dim/- cells from Treg-polarizing cultures was considerably higher. With treatment of atorvastatin, CD4+IL17+ cell population in cultures derived from SLE patients showed an increased susceptibility to CD95-induced apoptosis. However, the CD4+CD25+CD127dim/- cell population had reduced response to apoptosis. Accordingly, the ratio of transcription factor RORC/FoxP3 decreased in T cell cultures of SLE patients.

Conclusions Th17 cells were more resistant than Treg cells to CD95-induced apoptosis in SLE as compared to control subjects. Statins counteracted the dysregulated susceptibility of SLE T cells to apoptosis. Our findings reveal a novel mechanism underlying the imbalance of Th17/Treg and show a potential interest to the treatment of the patients with SLE.

Disclosure of Interest None declared

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