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- W2262637715 abstract "We previously showed that the immunosuppressant macrolide rapamycin (Sirolimus) effectively controlled SLE disease activity and normalized the high baseline calcium as well as the increased T cell receptor (TCR) stimulation-induced calcium fluxing in SLE T cells. Here, we document that mTOR activity is increased in SLE T cells and it is normalized by in vivo treatment with rapamycin, a specific inhibitor of mTOR kinase activity. We show increased phosphorylation of two targets of mTOR, ribosomal S6 kinase (S6K) and eukaryotic initiation factor 4E binding protein (4E-BP), in T cells from SLE patients. Healthy controls and patients treated with rapamycin in vivo did not show phosphorylation of these proteins. Levels of mTOR and of its binding partners, raptor and rictor, were similar in control and SLE T cells. SLE T cells are deficient in the TCR-associated proteins CD3ζ and Lck. It has been shown that correction of the CD3ζ deficiency by expression of exogenous CD3ζ in SLE T cells normalizes calcium homeostasis. Rapamycin treatment in vivo also normalizes calcium fluxing in SLE T cells, so we measured the levels of CD3ζ and Lck in T cells isolated from rapamycin-treated patients. T cells obtained from patients treated with rapamycin in vivo show significant recovery of these signaling molecules versus SLE patients not receiving rapamycin. Rapamycin is an efficacious treatment for SLE and normalizes calcium levels in SLE T cells, likely by restoring normal levels of T cell receptor-associated signaling molecules. This research was supported by the Alliance for Lupus Research and NIH grants AI-061066, AI-48079." @default.
- W2262637715 created "2016-06-24" @default.
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- W2262637715 date "2008-03-01" @default.
- W2262637715 modified "2023-10-15" @default.
- W2262637715 title "Increased activity of the mTOR pathway contributes to deficiencies of CD3ζ and Lck in T cells isolated from patients with systemic lupus erythematosus" @default.
- W2262637715 doi "https://doi.org/10.1096/fasebj.22.1_supplement.1074.20" @default.
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