Molecular landscape of CD8+ T cells in pure red cell aplasia
Yumei Liu1,2,3, Mengyuan Liu1,2,3, Xiaoman He1,2,3
1Department of Hematology, Tianjin Medical University General Hospital, No. 154 Anshandao Road, Heping District, Tianjin, 300052, China.
The aberrant function of lymphocytes is considered a significant contributing factor to pure red cell aplasia (PRCA), but the precise mechanism by which T lymphocytes induce erythroid development stagnation remains unclear. In our study, the CD8+ T lymphocytes were isolated from bone marrow aspirates of acquired PRCA patients and healthy controls. RNA sequencing (RNA-Seq) was performed to analyze gene expression profiles. Additionally, the expression levels of key molecules and transcription factors were assessed at the transcription and protein levels. The RNA-Seq analysis revealed a significant upregulation of genes associated with the PI3K/AKT/mTOR pathway in CD8+ T lymphocytes from patients with PRCA, compared to healthy controls. The mRNA expression of AKT, mTOR and key transcription factors T-bet were significantly upregulated in CD8+ T cells from patients with PRCA. Treatment with rapamycin, an mTOR inhibitor, attenuated the activation of CD8+ T lymphocytes in PRCA patients. Our findings demonstrate the activation of the PI3K/AKT/mTOR signaling pathway in CD8+ T lymphocytes of PRCA patients, suggesting its involvement in PRCA pathogenesis. Targeting this pathway may offer a potential therapeutic strategy for PRCA characterized by CD8+ T cell dysregulation.
The aberrant function of lymphocytes is considered a significant contributing factor to pure red cell aplasia (PRCA), but the precise mechanism by which T lymphocytes induce erythroid development stagnation remains unclear. In our study, the CD8+ T lymphocytes were isolated from bone marrow aspirates of acquired PRCA patients and healthy controls. RNA sequencing (RNA-Seq) was performed to analyze gene expression profiles. Additionally, the expression levels of key molecules and transcription factors were assessed at the transcription and protein levels. The RNA-Seq analysis revealed a significant upregulation of genes associated with the PI3K/AKT/mTOR pathway in CD8+ T lymphocytes from patients with PRCA, compared to healthy controls. The mRNA expression of AKT, mTOR and key transcription factors T-bet were significantly upregulated in CD8+ T cells from patients with PRCA. Treatment with rapamycin, an mTOR inhibitor, attenuated the activation of CD8+ T lymphocytes in PRCA patients. Our findings demonstrate the activation of the PI3K/AKT/mTOR signaling pathway in CD8+ T lymphocytes of PRCA patients, suggesting its involvement in PRCA pathogenesis. Targeting this pathway may offer a potential therapeutic strategy for PRCA characterized by CD8+ T cell dysregulation.
