Human dendritic cell-derived osteoclasts with high bone resorption capacity and T cell stimulation ability

Narisawa, Manabu; Kubo, Shunsuke; Okada, Yosuke; Yamagata, Kazuya; Nakayamada, Shingo; Sakata, Kimio; Yamaoka, Kunihiro; Tanaka, Yoshiya

doi:10.1016/j.bone.2020.115616

Cited by 25 publications

(17 citation statements)

References 26 publications

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“…Its mode of action is based on the inhibition of T-cell activation by binding to the costimulatory molecules CD80 and CD86 expressed by antigen-presenting cells such as DC. An interesting effect of abatacept is its capacity to inhibit the T-cell stimulatory capacities of osteoclasts differentiated from Mo-DC in the presence of M-CSF and RANKL [52]. Indeed, these DC-derived osteoclasts have the particularity of expressing MHC class II molecules as well as costimulatory molecules, and of retaining DC functions, such as the ability to stimulate T cells [52].…”

Section: Impact Of Targeted Therapies On Monocyte Differentiation Into Dendritic Cellsmentioning

confidence: 99%

“…An interesting effect of abatacept is its capacity to inhibit the T-cell stimulatory capacities of osteoclasts differentiated from Mo-DC in the presence of M-CSF and RANKL [52]. Indeed, these DC-derived osteoclasts have the particularity of expressing MHC class II molecules as well as costimulatory molecules, and of retaining DC functions, such as the ability to stimulate T cells [52]. So, by this double action on DC-derived osteoclasts, abatacept could prevent both osteoclastic bone resorption and aberrant activation of T cells.…”

Section: Impact Of Targeted Therapies On Monocyte Differentiation Into Dendritic Cellsmentioning

confidence: 99%

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Shaping of Monocyte-Derived Dendritic Cell Development and Function by Environmental Factors in Rheumatoid Arthritis

Coutant

2021

IJMS

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Dendritic cells (DC) are heterogeneous cell populations essential for both inducing immunity and maintaining immune tolerance. Chronic inflammatory contexts, such as found in rheumatoid arthritis (RA), severely affect the distribution and the function of DC, contributing to defective tolerance and fueling inflammation. In RA, the synovial fluid of patients is enriched by a subset of DC that derive from monocytes (Mo-DC), which promote deleterious Th17 responses. The characterization of environmental factors in the joint that impact on the development and the fate of human Mo-DC is therefore of great importance in RA. When monocytes leave the blood and infiltrate inflamed synovial tissues, the process of differentiation into Mo-DC can be influenced by interactions with soluble factors such as cytokines, local acidosis and dysregulated synoviocytes. Other molecular factors, such as the citrullination process, can also enhance osteoclast differentiation from Mo-DC, favoring bone damages in RA. Conversely, biotherapies used to control inflammation in RA, modulate also the process of monocyte differentiation into DC. The identification of the environmental mediators that control the differentiation of Mo-DC, as well as the underlying molecular signaling pathways, could constitute a major breakthrough for the development of new therapies in RA.

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Section: Impact Of Targeted Therapies On Monocyte Differentiation Into Dendritic Cellsmentioning

confidence: 99%

Section: Impact Of Targeted Therapies On Monocyte Differentiation Into Dendritic Cellsmentioning

confidence: 99%

Shaping of Monocyte-Derived Dendritic Cell Development and Function by Environmental Factors in Rheumatoid Arthritis

Coutant

2021

IJMS

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“…In vitro osteoclast formation of CD14 + blood monocytes from RA patients suggest pro-inflammatory monocytes differentiating into functional OCs in inflamed synovium [26]. Dendritic cells were also shown to be able to generate functional OCs [27,28], pointing out the potential contribution of various myeloid cells to functional osteoclasts in inflamed synovium. It is still not known if infiltrating cells in inflamed synovium fuse with cells, of maybe embryonic origin, that are already present in steady-state synovial tissue.…”

Section: Osteoclasts In Ramentioning

confidence: 96%

Novel Insights into the Ontogenetic and Functional Heterogeneity of Macrophages in Synovial Tissue and Bone

et al. 2021

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Inflammatory joint diseases like rheumatoid arthritis (RA) belong to the most prevalent autoimmune disorders. RA is characterized by a massive infiltration of immune cells into synovial tissue, cartilage destruction and bone erosion. The perpetuating inflammatory and destructive milieu is associated with severe pain and culminates in complete disability of synovial joints. The events initiating RA are still not fully understood and the treatments are mainly confined to strategies that modify and inhibit the body’s immune system. Macrophages and osteoclasts (OC) are myeloid cells of the innate immune system and are considered to play a central role in the inflammatory and destructive events of arthritis by production of inflammatory cytokines and mediating pathological bone resorption. In recent years, the use of novel fate mapping strategies identifying the origin and cellular development (ontogeny) of OC and macrophages in conjunction with new genetically modified mouse models, single cell analysis and advanced imaging techniques substantially changed our understanding on the ontogenetic and functional heterogeneity of these cells.

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“…Studies showed that DCs can trans-differentiate to OCs in the presence of RANKL and macrophage colony-stimulating factor (M-CSF) ( Figure 2C ) ( 35 , 118 ). Another study suggested that activated DCs (bone-marrow-derived and splenic CD11c + cells) upon interaction with T helper-cells (CD4 + T cells or Th) can develop into functional OCs (TRAP + CT-R + cathepsin-k + ) in RANKL/RANK-dependent manner ( Figure 2C ) ( 119 ).…”

Section: Cells Of the Myeloid Lineagementioning

confidence: 99%

Immunoporosis: Role of Innate Immune Cells in Osteoporosis

2021

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Osteoporosis or porous bone disorder is the result of an imbalance in an otherwise highly balanced physiological process known as ‘bone remodeling’. The immune system is intricately involved in bone physiology as well as pathologies. Inflammatory diseases are often correlated with osteoporosis. Inflammatory mediators such as reactive oxygen species (ROS), and pro-inflammatory cytokines and chemokines directly or indirectly act on the bone cells and play a role in the pathogenesis of osteoporosis. Recently, Srivastava et al. (Srivastava RK, Dar HY, Mishra PK. Immunoporosis: Immunology of Osteoporosis-Role of T Cells. Frontiers in immunology. 2018;9:657) have coined the term “immunoporosis” to emphasize the role of immune cells in the pathology of osteoporosis. Accumulated pieces of evidence suggest both innate and adaptive immune cells contribute to osteoporosis. However, innate cells are the major effectors of inflammation. They sense various triggers to inflammation such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), cellular stress, etc., thus producing pro-inflammatory mediators that play a critical role in the pathogenesis of osteoporosis. In this review, we have discussed the role of the innate immune cells in great detail and divided these cells into different sections in a systemic manner. In the beginning, we talked about cells of the myeloid lineage, including macrophages, monocytes, and dendritic cells. This group of cells explicitly influences the skeletal system by the action of production of pro-inflammatory cytokines and can transdifferentiate into osteoclast. Other cells of the myeloid lineage, such as neutrophils, eosinophils, and mast cells, largely impact osteoporosis via the production of pro-inflammatory cytokines. Further, we talked about the cells of the lymphoid lineage, including natural killer cells and innate lymphoid cells, which share innate-like properties and play a role in osteoporosis. In addition to various innate immune cells, we also discussed the impact of classical pro-inflammatory cytokines on osteoporosis. We also highlighted the studies regarding the impact of physiological and metabolic changes in the body, which results in chronic inflammatory conditions such as ageing, ultimately triggering osteoporosis.

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Human dendritic cell-derived osteoclasts with high bone resorption capacity and T cell stimulation ability

Cited by 25 publications

References 26 publications

Shaping of Monocyte-Derived Dendritic Cell Development and Function by Environmental Factors in Rheumatoid Arthritis

Shaping of Monocyte-Derived Dendritic Cell Development and Function by Environmental Factors in Rheumatoid Arthritis

Novel Insights into the Ontogenetic and Functional Heterogeneity of Macrophages in Synovial Tissue and Bone

Immunoporosis: Role of Innate Immune Cells in Osteoporosis

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