Insensitive to PTH of CD8⁺ T cells regulate bone marrow mesenchymal stromal cell in aplastic anemia patients

Abstract

Aplastic anemia (AA) is a rare disorder characterized by the suppression of bone marrow function resulting in progressive pancytopenia. The pathogenesis of AA is complex and involves an abnormal hematopoietic microenvironment, hematopoietic stem cell/progenitor cell deficiencies, and immunity disorders. However, the underlying mechanism of the disease is still not fully uncovered. In this research, we collected both donor and patient samples and found suppressed proliferation, abnormal differentiation as well as increased apoptosis of patient mesenchymal stem cells (MSCs). Considering the close relationship of parathyroid hormone (PTH) and MSCs differentiation, further studies showed that although patients maintained normal serum PTH level, their CD8⁺ T cells possessed lower PTH receptors. The insensitive to PTH of patients' CD8⁺ T cells finally lead to reduced expression of key Wnt factors. In all, bone marrow CD8⁺ T cells may play an important role in inducing MSCs adipogenesis and osteogenesis imbalancement.