Role of macrophages and phagocytes in orchestrating normal and pathologic hematopoietic niches

Lévesque, Jean‐Pierre; Summers, Kim M.; Millard, Susan; Bisht, Kavita; Pettit, Allison R.

doi:10.1016/j.exphem.2021.07.001

Cited by 11 publications

(8 citation statements)

References 181 publications

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“…Despite the absence of hematopoietic island macrophages in the fetal liver and bone marrow, which function in regulation of erythropoiesis and myelopoiesis (see Fig. 1 ) [ 82 , 83 ], the mutant animals are not anemic and there is no accumulation of expelled red cell nuclei in the fetal liver. So, to some extent, amateurs must also fulfill some of the tasks normally undertaken by macrophages and OCL in bone development and hematopoiesis.…”

Section: Csf1r Signals In Bone Developmentmentioning

confidence: 99%

CSF1R as a Therapeutic Target in Bone Diseases: Obvious but Not so Simple

Hume

Batoon

Sehgal

et al. 2022

Curr Osteoporos Rep

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Purpose of Review The purpose of the review is to summarize the expression and function of CSF1R and its ligands in bone homeostasis and constraints on therapeutic targeting of this axis. Recent Findings Bone development and homeostasis depends upon interactions between mesenchymal cells and cells of the mononuclear phagocyte lineage (MPS), macrophages, and osteoclasts (OCL). The homeostatic interaction is mediated in part by the systemic and local production of growth factors, macrophage colony-stimulating factor (CSF1), and interleukin 34 (IL34) that interact with a receptor (CSF1R) expressed exclusively by MPS cells and their progenitors. Loss-of-function mutations in CSF1 or CSF1R lead to loss of OCL and macrophages and dysregulation of postnatal bone development. MPS cells continuously degrade CSF1R ligands via receptor-mediated endocytosis. As a consequence, any local or systemic increase or decrease in macrophage or OCL abundance is rapidly reversible. Summary In principle, both CSF1R agonists and antagonists have potential in bone regenerative medicine but their evaluation in disease models and therapeutic application needs to carefully consider the intrinsic feedback control of MPS biology.

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Section: Csf1r Signals In Bone Developmentmentioning

confidence: 99%

CSF1R as a Therapeutic Target in Bone Diseases: Obvious but Not so Simple

Hume

Batoon

Sehgal

et al. 2022

Curr Osteoporos Rep

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“…The effect of innate immune stimulation on BM erythropoiesis has previously been studied in nonautoimmune mice in which LPS suppresses erythropoiesis at the CFU-E/ProEB stage, while enhancing stress erythropoiesis through induction of SpiC. Similar findings have been observed in response to exogenous administration of G-CSF and Flt3 ligands ( Bisht et al, 2020 ; Tay et al, 2020 ; Lévesque et al, 2021 ). Flt3 ligand is known to be up-regulated in the BMs of Yaa mice ( Adachi et al, 2002 ) and T cells expressing membrane Flt3 ligand have been reported in the BMs of lupus patients with aplastic anemia ( Pfister et al, 2000 ).…”

Section: Discussionmentioning

confidence: 58%

Human TLR8 induces inflammatory bone marrow erythromyeloblastic islands and anemia in SLE-prone mice

et al. 2023

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Anemia commonly occurs in systemic lupus erythematosus, a disease characterized by innate immune activation by nucleic acids. Overactivation of cytoplasmic sensors by self-DNA or RNA can cause erythroid cell death, while sparing other hematopoietic cell lineages. Whereas chronic inflammation is involved in this mechanism, less is known about the impact of systemic lupus erythematosus on the BM erythropoietic niche. We discovered that expression of the endosomal ssRNA sensor human TLR8 induces fatal anemia in Sle1.Yaa lupus mice. We observed that anemia was associated with a decrease in erythromyeloblastic islands and a block in differentiation at the CFU-E to proerythroblast transition in the BM. Single-cell RNAseq analyses of isolated BM erythromyeloblastic islands from human TLR8-expressing mice revealed that genes associated with essential central macrophage functions including adhesion and provision of nutrients were down-regulated. Although compensatory stress erythropoiesis occurred in the spleen, red blood cell half-life decreased because of hemophagocytosis. These data implicate the endosomal RNA sensor TLR8 as an additional innate receptor whose overactivation causes acquired failure of erythropoiesis via myeloid cell dysregulation.

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“…Among others, monocytes are pivotal in the pathophysiology of MM and its resistance to treatment. 24 Tumor-associated monocytes and macrophages promote tumor proliferation and metastasis by protecting the tumor from invasion by T- and NK-lymphocytes. 25 Monocytes in breast cancer, colon cancer, and hepatocellular carcinoma have weakened immune activity.…”

Section: Discussionmentioning

confidence: 99%

CD73 Dysregulates Monocyte Anti-Tumor Activity in Multiple Myeloma

Zhou¹,

Liu²,

Guan³

et al. 2023

CMAR

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Purpose Multiple myeloma (MM) is characterized by immune cell dysfunction in the tumor microenvironment (TME). We aimed at evaluating the effect of CD73, an overexpressed factor in some tumors, on anti-tumor immune function in the TME of MM. Patients and Methods We analyzed the expression of CD73 in T-, B-, and natural killer (NK)-lymphocytes and monocytes in bone marrow (BM), peripheral blood (PB) from MM patients and healthy controls, and residual CD138+ cells using flow cytometry. The anti-tumor activity of these monocytes was confirmed by co-culture with RPMI-8226 cells treated with a CD73 inhibitor. We determined the interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ levels using a cytometric bead array. Monocyte phagocytosis in cell culture sediment was then observed and measured. Results CD73 was highly expressed in T-, B-, and NK-lymphocytes and monocytes from the BM and PB isolated from patients with MM. Compared with healthy controls, MM samples exhibited significantly higher CD73 expression and TNF-α, IFN-γ, IL-10 levels in monocytes. Inhibiting CD73 in BM immune cells from MM samples significantly increased the secretion of IL-2, TNF-α, and IFN-γ, as well as the killing ability of immune cells. However, monocyte phagocytosis was seldom observed. Inhibiting CD73 in MM monocytes significantly increased the secretion of IL-2, TNF-α, and IFN-γ in monocytes and improved monocyte killing and phagocytosis. Conclusion Monocytes from MM exhibited weakened anti-tumor effects, and CD73 was involved in forming an immunosuppressive microenvironment. Inhibiting CD73 partly restored the anti-tumor activity of monocytes, a potential strategy for the treatment of MM.

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Role of macrophages and phagocytes in orchestrating normal and pathologic hematopoietic niches

Cited by 11 publications

References 181 publications

CSF1R as a Therapeutic Target in Bone Diseases: Obvious but Not so Simple

CSF1R as a Therapeutic Target in Bone Diseases: Obvious but Not so Simple

Human TLR8 induces inflammatory bone marrow erythromyeloblastic islands and anemia in SLE-prone mice

CD73 Dysregulates Monocyte Anti-Tumor Activity in Multiple Myeloma

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