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30 Metabolic reprogramming in cd4+cd28-cxcr3intt-bethi cells and its relevance to pathogenesis in patients with sle
  1. S Iwata1,
  2. K Sakata1,
  3. M Hajime1,
  4. M Zhang1,
  5. M Torigoe1,2,
  6. N Ohkubo1,
  7. S Nakayamada1 and
  8. Y Tanaka1
  1. 1University of Occupational and Environmental Health, The First Depertment of Internal Medicine, Kitakyushu, Japan
  2. 2Department of Endocrinology- Metabolism- Rheumatology and Nephrology, Faculty of Medicine- Oita University- Yufu- Oita- Japan, Yufu, Japan

Abstract

Background and Aims CD4+ T cells play a crucial role in pathological process of Systemic Lupus Erythematosus (SLE). Recently, we found that T-bet is an important factor for shift to glycolysis in activated CD4+ T cells in vitro. In this study, we examined the mechanism by which T-bet in CD4+ T cells involved in pathogenesis of SLE.

Methods Peripheral blood mononuclear cells were obtained from 19 healthy controls (HCs), 30 patients with bio-naïve active RA and 60 patients with SLE. The expression of CXCR3, T-bet, mTORC1 phosphorylation and IFN-γ production in CD4+ T cells were measured by flow cytometry, and assessed the association with clinical characteristics.

Results We found that the ratio of CD28-CXCR3intT-bethi cells in patients with SLE was significantly higher compared to HCs. CD4+CD28-CXCR3intT-bethi cells mainly consisted of CD45RA-CCR7- effector memory cells and were significantly activated with pronounced IFN-γ production. Interestingly, the ratio of CD4+CD28-CXCR3intT-bethi cells was significantly correlated with the number of immunosuppressants previously used for the SLE patients, that is treatment-resistant. Phosphorylation of mTORC1, which is important for shift to glycolysis, in CD4+ T cells from patients with SLE was significantly increased compared to HCs. T-bet expression was significantly correlated with mTOC1 phosphorylation and IFN-γ production in CD4+ T cells from patients with SLE.

Conclusions These results indicated that CD4+CD28-CXCR3intT-bethi cells might be related to refractory to established therapies in patients with SLE. In addition, these cells are constitutively activated accompanied with shift to glycolysis through IFN-γ-mTORC1-T-bet pathway, which is a potential target for patients with SLE.

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