Dysfunctional T cells due to the abnormal glucose metabolism in patients with primary immune thrombocytopenia

To investigate T-cell glucose metabolism dysfunction in primary immune thrombocytopenia (ITP) and the role of mammalian target of rapamycin complex 1 (mTORC1) in regulatory T-cell (Treg) suppression function. Gene set enrichment analysis (GSEA) assessed glycolysis and mTORC1 pathways in dysfunctional Tregs from patients with systemic lupus erythematosus (SLE). CD4⁺ effector T cells (Teffs) were isolated from peripheral blood mononuclear cells (PBMCs) pre- and post-dexamethasone treatment and from healthy controls. The extracellular acidification rate (ECAR) of Tregs and Teffs was measured using the Agilent Seahorse XF96 platform. Flow cytometry evaluated glucose transporter 1 (GLUT1) and phosphorylated S6 (p-S6) expression. The immune suppression function of Tregs was assessed by mTORC1 inhibiting test. GSEA revealed a possible relation of glycolysis and mTORC1 signalling in dysfunctional Tregs. Both Tregs and Teffs from ITP patients showed elevated ECAR, with Teff ECAR normalizing post-glucocorticoid treatment. Treg ECAR decreased after treatment, but remained higher than normal level. GLUT1 and p-S6 expression was significantly higher in ITP Tregs and Teffs, normalizing GLUT1 levels after glucocorticoid therapy. Inhibiting mTORC1 could recover the suppression of ITP Tregs. Dysregulated CD4⁺ T-cell glucose metabolism contributes to ITP pathogenesis. Targeting mTORC1 signal may offer a novel therapeutic approach for ITP.