Human MDSCs derived from the bone marrow maintain their functional ability but have a reduced frequency of induction in
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SHORT REPORT
Open Access
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 Magri1†, Elena Masetto2†, Samantha Solito1,3, Samuela Francescato4, Elisa Belluzzi1, Assunta Pozzuoli1, Antonio Berizzi1,5, Pietro Ruggieri1,5 and Susanna Mandruzzato1,2*
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. Keywords: MDSCs, Aging, Immunosuppression
Background Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immunosuppressive myeloid cells developing from myeloid progenitors, which are particularly enriched in pathological conditions such as cancer, infections, inflammation and sepsis [1–3]. These pathological * Correspondence: [email protected] † Sara Magri and Elena Masetto contributed equally to this work. 1 Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Gattamelata, 64, 35128 Padova, Italy 2 IOV-IRCCS, Padova, Italy Full list of author information is available at the end of the article
conditions determine an increase in circulating colonystimulating factors (CSFs) as well as chemokines that stimulate the myelopoiesis and, consequently, the generation of immature MDSCs. Different subsets of human MDSCs have been documented in several types of tumors, and it appears that all MDSC phenotypes can be allocated to one of the three main subsets, each of them containing more than one cell population. Monocytic MDSCs (MMDSCs) share the morphology
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