Dysregulation of apolipoprotein o reprograms CCR7+CD4+T cell fate in primary autoimmune thrombocytopenia.

Primary immune thrombocytopenia involves antibody-driven platelet loss and perturbed CD4+ T cell regulation. By integrating single-cell transcriptomic, epigenetic, and functional analyses, we delineated CCR7+CD4+ T cell states with distinct metabolic and transcriptional programs. A subset enriched in patients exhibited reduced oxidative phosphorylation and enhanced glycolysis, accompanied by elevated expression of SP100 and its downstream transcriptional targets FOXP1 and CDK6. Trajectory analysis positioned these cells as developmentally arrested intermediates that, in normal individuals, mature into CCR7+ cells expressing apolipoprotein O (APOO). Functional perturbations revealed that APOO preserves oxidative metabolism and CCR7 identity while restraining SP100-dependent transcription. Methylation profiling identified APOO hypermethylation and transcriptional silencing in patient-derived CD4+ T cells. Together, these data define APOO as a metabolic-transcriptional checkpoint governing CCR7+CD4+ T cell fate, whose repression fosters dysfunctional differentiation and immune imbalance in autoimmune thrombocytopenia.