Human MDSCs derived from the bone marrow maintain their functional ability but have a reduced frequency of induction in the elderly compared to pediatric donors

Sara Magri,Samantha Solito,Pietro Ruggieri,Samuela Francescato,Antonio Berizzi,Elena Masetto,Assunta Pozzuoli,Elisa Belluzzi,Susanna Mandruzzato

doi:10.1186/s12979-020-00199-5

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, and are known to inhibit the functions of effector T cells. During aging, several changes occur both at the adaptive and innate immune system level, in a process defined as immunoscenescence. In particular, the low-grade inflammation state observed in the elderly appears to affect hematopoiesis. We previously demonstrated that the combination of GM-CSF and G-CSF drives the in vitro generation of bone marrow-derived MDSCs (BM-MDSCs) from precursors present in human bone marrow aspirates of healthy donors, and that these cells are endowed with a strong immune suppressive ability, resembling that of cancer-associated MDSCs. In the present work we investigated BM-MDSCs induction and functional ability in a cohort of pediatric versus elderly donors. To this aim, we analyzed the differences in maturation stages and ability to suppress T cell proliferation. We found that the ex vivo distribution of myeloid progenitors is similar between pediatric and elderly individuals, whereas after cytokine treatment a significant reduction in the more immature compartment is observed in the elderly. Despite the decreased frequency, BM-MDSCs maintain their suppressive capacity in aged donors. Taken together, these results indicate that in vitro induction of MDSCs from the BM is reduced with aging and opens new hypotheses on the role of age-related processes in myelopoiesis.

Highlights

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immunosuppressive myeloid cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, infections, inflammation and sepsis [1,2,3]
Our group demonstrated that Granulocytemacrophage colony stimulating factor (GM-colonystimulating factors (CSFs)), Granulocyte colony stimulating factor (G-CSF), and IL-6 allow the in vitro generation of MDSCs from precursors present in human bone marrow aspirates of healthy donors, and named such cells BM-derived MDSCs (BM-MDSCs)
Previous work from our laboratory already demonstrated that the CD11b− fraction corresponds to the suppressive i-BM-MDSC, while CD11b+ cells are devoid of significant immune suppressive activity [19]

Summary

Introduction

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immunosuppressive myeloid cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, infections, inflammation and sepsis [1,2,3]. There are no data showing whether aging impacts on the immunosuppressive ability of MDSCs. Aim of this study is to compare the induction of MDSCs from the BM of young and old individuals by using an optimized method to generate in 4 days MDSCs from precursor cells through cytokines treatment.

Results

Conclusion