30 Metabolic reprogramming in cd4+cd28-cxcr3intt-bethi cells and its relevance to pathogenesis in patients with sle

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-naive 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 - CXCR3 int T-bet hi cells in patients with SLE was significantly higher compared to HCs. CD4 + CD28 - CXCR3 int T-bet hi cells mainly consisted of CD45RA - CCR7 - effector memory cells and were significantly activated with pronounced IFN-γ production. Interestingly, the ratio of CD4 + CD28 - CXCR3 int T-bet hi 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 - CXCR3 int T-bet hi 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.