Regulatory T cells in the bone marrow microenvironment: homeostatic crosstalk, disease remodeling, and therapeutic opportunities

Regulatory T cells (Tregs) help maintain immune balance in hematopoietic niches by interacting with the bone marrow microenvironment. Under normal conditions, surrounding cells send signals that affect Treg movement, their length of stay in the bone marrow, their number and activity. In turn, Tregs affect hematopoietic stem cells, mesenchymal stromal cells, and other immune cells through direct contact or factors they release. When this balance is disturbed, Treg numbers and functions may change according to the disease condition, and these changes are related to the development and progression of multiple myeloma, myelodysplastic syndromes, acute myeloid leukemia, aplastic anemia, and immune thrombocytopenia. Epigenetic changes and other molecular abnormalities may further disturb this communication and allow the abnormal state to continue. Current investigational treatment methods mainly aim to increase Treg numbers, selectively remove certain Tregs, or adjust their functions by targeting the bone marrow environment. This review summarizes existing evidence about these interactions, explains how they become abnormal, and discusses their potential value in restoring normal blood cell production and immune balance.