Macrophages and osteoclasts stem from a bipotent progenitor downstream of a macrophage/osteoclast/dendritic cell progenitor

Xiao, Yanling; Palomero, Jara; Grabowska, Joanna; Wang, Liqin; Rink, Iris de; Helvert, Luuk van; Borst, Jannie

doi:10.1182/bloodadvances.2017008540

Cited by 39 publications

(42 citation statements)

References 45 publications

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“…Whereas, MN, Mϕ, and DC origin has been widely explored, the origin of OCLs remained more elusive and OCLs are usually forgotten in hematopoietic lineage trees. However, in adults a common early bone marrow (BM) progenitor for OCLs and other monocytic cells (Mϕ/OCL/DC progenitor, MODP) has been identified downstream of the granulocyte/Mϕ progenitor (GMP) (Figure 2) (39, 40). In human, CD11b − CD34 + c-KIT + FLT3 + IL-3Rα low BM cells are common progenitors for Mϕs, DCs, OCLs and granulocytes.…”

Section: Diversity In Osteoclast Originmentioning

confidence: 99%

Immune Function and Diversity of Osteoclasts in Normal and Pathological Conditions

et al. 2019

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Osteoclasts (OCLs) are key players in controlling bone remodeling. Modifications in their differentiation or bone resorbing activity are associated with a number of pathologies ranging from osteopetrosis to osteoporosis, chronic inflammation and cancer, that are all characterized by immunological alterations. Therefore, the 2000s were marked by the emergence of osteoimmunology and by a growing number of studies focused on the control of OCL differentiation and function by the immune system. At the same time, it was discovered that OCLs are much more than bone resorbing cells. As monocytic lineage-derived cells, they belong to a family of cells that displays a wide heterogeneity and plasticity and that is involved in phagocytosis and innate immune responses. However, while OCLs have been extensively studied for their bone resorption capacity, their implication as immune cells was neglected for a long time. In recent years, new evidence pointed out that OCLs play important roles in the modulation of immune responses toward immune suppression or inflammation. They unlocked their capacity to modulate T cell activation, to efficiently process and present antigens as well as their ability to activate T cell responses in an antigen-dependent manner. Moreover, similar to other monocytic lineage cells such as macrophages, monocytes and dendritic cells, OCLs display a phenotypic and functional plasticity participating to their anti-inflammatory or pro-inflammatory effect depending on their cell origin and environment. This review will address this novel vision of the OCL, not only as a phagocyte specialized in bone resorption, but also as innate immune cell participating in the control of immune responses.

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Section: Diversity In Osteoclast Originmentioning

confidence: 99%

Immune Function and Diversity of Osteoclasts in Normal and Pathological Conditions

et al. 2019

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“…Many genetic associations lack replication, with the exception of CX3CR1 (encoding the G protein-coupled receptor CX3-chemokine receptor 1 (CX3CR1); also known as fractalkine), which was first identified by linkage mapping and exome sequencing 62,63 , with a single nucleotide polymorphism (SNP) being subsequently linked independently with DDH 64 . CX3CR1 is involved in mesenchymal stem cell recruitment to the joint 62,65 , and Cx3cr1-knockout mice develop acetabular dysplasia 66 . The association between DDH and GDF5 has also been replicated in a GWAS using data from the UK Biobank 67 .…”

Section: Ortolani Testmentioning

confidence: 99%

Spontaneous dog osteoarthritis — a One Medicine vision

et al. 2019

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| Osteoarthritis (OA) is a global disease that, despite extensive research, has limited treatment options. Pet dogs share both an environment and lifestyle attributes with their owners, and a growing awareness is developing in the public and among researchers that One Medicine, the mutual co-study of animals and humans, could be beneficial for both humans and dogs. To that end, this Review highlights research opportunities afforded by studying dogs with spontaneous OA , with a view to sharing this active area of veterinary research with new audiences. Similarities and differences between dog and human OA are examined, and the proposition is made that suitably aligned studies of spontaneous OA in dogs and humans, in particular hip and knee OA , could highlight new avenues of discovery. Developing cross-species collaborations will provide a wealth of research material and knowledge that is relevant to human OA and that cannot currently be obtained from rodent models or experimentally induced dog models of OA. Ultimately , this Review aims to raise awareness of spontaneous dog OA and to stimulate discussion regarding its exploration under the One Medicine initiative to improve the health and well-being of both species.

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“…A subpopulation of bone marrow myeloid cells expresses CD115, the macrophage colony-stimulating factor (M-CSF) receptor. This population consists of monocytes and “common progenitors of conventional and plasmacytoid dendritic cells” (11), which can further differentiate into macrophages, DCs and osteoclasts (12). CD115+ monocytes/common myeloid progenitors and their progeny exhibit important functions for the maintenance of hematopoietic stem and progenitor cells in the bone marrow, innate and adaptive immunity, wound healing and bone homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10

et al. 2019

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Bone marrow plasma cells have been reported to represent a major source of IL-10; however, the impact of plasma cell derived IL-10 in that tissue remains poorly understood. We confirm in this study that even in the absence of acute immune reactions, mature plasma cells represent the dominant IL-10+ cell population in the bone marrow, and identify myeloid-lineage cells as a main local target for plasma cell derived IL-10. Using Vert-X IL-10 transcriptional reporter mice, we found that more than 50% of all IL-10+ cells in bone marrow were CD138+ plasma cells, while other IL-10+ B lineage cells were nearly absent in this organ. Accordingly, IL-10 was found in the supernatants of short-term cultures of FACS-sorted bone marrow plasma cells, confirming IL-10 secretion from these cells. IL-10+ bone marrow plasma cells showed a B220−/CD19−/MHCII low phenotype suggesting that these cells represent a mature differentiation stage. Approximately 5% of bone marrow leucocytes expressed the IL-10 receptor (IL-10R), most of them being CD115+/Ly6C+/CD11c− monocytes. Compared to littermate controls, young B lineage specific IL-10 KO mice showed increased numbers of CD115+ cells but normal populations of other myeloid cell types in bone marrow. However, at 7 months of age B lineage specific IL-10 KO mice exhibited increased populations of CD115+ myeloid and CD11c+ dendritic cells (DCs), and showed reduced F4/80 expression in this tissue; hence, indicating that bone marrow plasma cells modulate the differentiation of local myeloid lineage cells via IL-10, and that this effect increases with age. The effects of B cell/plasma cell derived IL-10 on the differentiation of CD115+, CD11c+, and F4/80+ myeloid cells were confirmed in co-culture experiments. Together, these data support the idea that IL-10 production is not limited to early plasma cell stages in peripheral tissues but is also an important feature of mature plasma cells in the bone marrow. Moreover, we provide evidence that already under homeostatic conditions in the absence of acute immune reactions, bone marrow plasma cells represent a non-redundant source for IL-10 that modulates local myeloid lineage differentiation. This is particularly relevant in older individuals.

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Macrophages and osteoclasts stem from a bipotent progenitor downstream of a macrophage/osteoclast/dendritic cell progenitor

Cited by 39 publications

References 45 publications

Immune Function and Diversity of Osteoclasts in Normal and Pathological Conditions

Immune Function and Diversity of Osteoclasts in Normal and Pathological Conditions

Spontaneous dog osteoarthritis — a One Medicine vision

Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10

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