Age-related expansion and increased osteoclastogenic potential of myeloid-derived suppressor cells. (September 2021)

• Record Type: Journal Article
• Authors: Li, Zhaofei; Zhao, Yanfang; Chen, Zhu; Katz, Jannet; Michalek, Suzanne M.; Li, Yuhong; Zhang, Ping
• Is Part Of: Molecular immunology. Volume 137(2021)
• Page Start: 187
• Page End: 200
• Publication Date: 2021-09
• Subjects: Arg1 arginase 1 -- BV/TV bone volume/tissue volume -- BM bone marrow -- HSCs hematopoietic stem cells -- iNOS inducible nitric oxide synthase -- LPS lipopolysaccharide -- M-CSF macrophage colony stimulating factor -- MDSCs myeloid-derived suppressor cells -- MO-MDSCs monocytic or mononuclear MDSCs -- MNCs multinucleated cells -- Oc.S/BS osteoclast surface/bone surface -- PMN-MDSCs granulocytic or polymorphonuclear MDSCs -- pStat3 phosphorylated signal transducer and activator of transcription 3 -- RANKL receptor activator of NF-B ligand -- Tb.N trabecular number -- Tb.Sp trabecular separation -- TRAP tartrate-resistant acid phosphatase -- WGA wheat germ agglutinin; Aging -- MDSCs -- Osteoclast precursors -- Bone loss; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2021.07.004
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Aging is associated with increased accumulation of MDSCs in bone marrow and periphery. Aging increases the osteoclastogenic potential of monocytic MDSCs in vitro and in vivo . Monocytic MDSCs are a source of osteoclast precursors and contribute to age-associated bone loss. Low-grade inflammation associated with aging increases the sensitivity of monocytic MDSCs to RANKL-induced osteoclastogenesis. Abstract: Aging is associated with excessive bone loss that is not counteracted with the development of new bone. However, the mechanisms underlying age-related bone loss are not completely clear. Myeloid-derived suppressor cells (MDSCs) are a population of heterogenous immature myeloid cells with immunosuppressive functions that are known to stimulate tumor-induced bone lysis. In this study, we investigated the association of MDSCs and age-related bone loss in mice. Our results shown that aging increased the accumulation of MDSCs in the bone marrow and spleen, while in the meantime potentiated the osteoclastogenic activity of the CD11b + Ly6C hi Ly6G + monocytic subpopulation of MDSCs. In addition, CD11b + Ly6C hi Ly6G + MDSCs from old mice exhibited increased expression of c-fms compared to young mice, and were more sensitive to RANKL-induced osteoclast gene expression. On the other hand, old mice showed elevated production of IL-6 and receptor activator of nuclear factor kappa-B ligand (RANKL) in the circulation. Furthermore, IL-6 and RANKL were able to induce the proliferation of CD11b + Ly6C hi Ly6G + MDSCs and up-regulate c-fms expression. Moreover, CD11b + Ly6C hi Ly6G + MDSCs obtained from old mice showed increased antigen-specific T cell suppressive function, pStat3 expression, and cytokine production in response to inflammatory stimulation, compared to those cells obtained from young mice. Our findings suggest that CD11b + Ly6C hi Ly6G + MDSCs are a source of osteoclast precursors that together with the presence of persistent, low-grade inflammation, contribute to age-associated bone loss in mice.