Bone Marrow Immunity and Myelodysplasia

Abstract

Myelodysplastic syndrome (MDS) is characterized by an ineffective hematopoiesis with production of aberrant clones and a high cell apoptosis rate in bone marrow (BM). Macrophages are in charge of phagocytosis. Innate Immune cells and specific T cells are in charge of immunosurveillance. Little is known on BM cell recruitment and activity as BM aspirate is frequently contaminated with peripheral blood. But evidences suggest an active role of immune cells in protection against MDS and secondary leukemia. BM CD8+ CD28− CD57+ T cells are directly cytotoxic and have a distinct cytokine signature in MDS, producing TNF-α, IL-6, CCL3, CCL4, IL-1RA, TNFα, FAS-L, TRAIL, and so on. These tools promote apoptosis of aberrant cells. On the other hand, they also increase MDS-related cytopenia and myelofibrosis together with TGFβ. IL-32 produced by stromal cells amplifies NK cytotoxicity but also the vicious circle of TNFα production. Myeloid-derived suppressing cells (MDSC) are increased in MDS and have ambiguous role in protection/progression of the diseases. CD33 is expressed on hematopoietic stem cells on MDS and might be a potential target for biotherapy. MDS also has impact on immunity and can favor chronic inflammation and emergence of autoimmune disorders. BM is the site of hematopoiesis and thus contains a complex population of cells at different stages of differentiation from stem cells and early engaged precursors up to almost mature cells of each lineage including erythrocytes, megakaryocytes, myelo-monocytic cells (monocyte/macrophage and granulocytes), NK cells, and B cells. Monocytes and B cell finalize their maturation in peripheral tissues or lymph nodes after migration through the blood. On the other hand, T cells develop in thymus and are present in BM only as mature cells, just like other well vascularized tissues. BM precursors have a strong proliferative capacity, which is usually associated with a high risk for genetic errors, cell dysfunction, and consequent cell death. Abnormal cells are prone to destruction through spontaneous apoptosis or because of the immunosurveillance that needs to stay highly vigilant. High rates of proliferation or differentiation failures lead to a high rate of cell death and massive release of debris to be captured and destroyed (1). Numerous macrophages reside in BM in charge of home-keeping. They have a high capacity of phagocytosis required for clearing all these debris.

Melanomacrophage functions in the liver of the caecilian Siphonops annulatus

“…Other mechanisms might be involved with the phagocytosis of basophils, such as one responsible for the elimination of senescent or defective cells from the hematopoietic tissue (Lambert et al. ). Regardless of the actual physiological process that culminated in the referred phagocytosis, it seems that the current study is the first to capture the basophil phagocytosis by melanomacrophages.…”

Clinical Implication of Multi-Parameter Flow Cytometry in Myelodysplastic Syndromes

“…Increased frequencies of MDSCs and T-regulatory cells are thought to reflect an immunosuppressive environment in high risk MDS [2,26]. The immunophenotype of MDSCs in humans, however, is not yet fully agreed upon [27].…”

“…The knowledge on and management of myelodysplastic syndromes (MDS) have taken a flight over the past decades; major parts of the pathobiology have been elucidated, several additional diagnostic and prognostic tools implemented and novel therapies discovered [1][2][3][4][5][6]. Nevertheless, MDS are still a challenging group of diseases, mostly due to their extensive heterogeneity and often non-clear-cut diagnosis [7,8].…”

The role of monocytosis and neutrophilia in atherosclerosis

“…In inflammation, these progenitors were shown to be primarily involved in the mobilization of pro‐inflammatory cells . Cholesterol metabolism regulates the function of HSPCs and their ability to differentiate to monocytes and other immune cells.…”