Generation of CD1+RelB+ dendritic cells and tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated giant cells from human monocytes

Akagawa, Kiyoko S.; Takasuka, Naomi; Nozaki, Yuko; Komuro, Iwao; Azuma, Miyuki; Ueda, Masamichi; Naito, Makoto; Takahashi, Kiyoshi

doi:10.1182/blood.v88.10.4029.bloodjournal88104029

Cited by 191 publications

(64 citation statements)

References 37 publications

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“…GM-CSF and IL-4 function by downregulating CD14 on PBMC at a transcriptional level [60,61]. Culturing human PBMC with GM-CSF, IFN-c and IL-4 skews the differentiation of monocytes to functional DC, which are not terminally differentiated but capable of presenting antigen to T cells [62][63][64][65]. Human monocyte-enriched PBMC cultured with only M-CSF differentiate into immature MU but, with the addition of GM-CSF and IL-4, convert to immature MDDC.…”

Section: Monocyte Differentiation In Steady Statementioning

confidence: 99%

“…Though culture with M-CSF or GM-CSF can both result in MU differentiation, MU obtained with different treatments exhibit different morphology. M-CSF-stimulated MU (M-BMM) exhibit a spindle-shaped morphology, while GM-CSF-derived MU (GM-BMM) appear more rounded [64,66].…”

Section: Monocyte Differentiation In Steady Statementioning

confidence: 99%

“…Inflammatory stimuli, such as LPS, combined with GM-CSF and IL-4 result in the maturation and irreversible commitment of MDDC to mature DCs [64,69]. Addition of TNF to immature DC in vitro reduces their APC capacity, possibly making them functionally mature [62].…”

Section: Inflammatory Signals and Monocyte Differentiationmentioning

confidence: 99%

“…Stromal cells like fibroblasts have been shown to impact upon this differentiation. Although monocytes cultured with GM-CSF and IL-4 yield DC [64], the coculture of these cells with fibroblasts in steady-state conditions, skews the differentiation to MU. Monocytes, which become activated when they cross the endothelium, secrete M-CSF and stimulate the release of IL-6 from fibroblasts.…”

Section: Effect Of Resident Cells On Monocyte Differentiationmentioning

confidence: 99%

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The plasticity of inflammatory monocyte responses to the inflamed central nervous system

Ashhurst

Vreden

Niewold

et al. 2014

Cellular Immunology

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Over the last three decades it has become increasingly clear that monocytes, originally thought to have fixed, stereotypic responses to foreign stimuli, mediate exquisitely balanced protective and pathogenic roles in disease and immunity. This balance is crucial in core functional organs, such as the central nervous system (CNS), where minor changes in neuronal microenvironments and the production of immune factors can result in significant disease with fatal consequences or permanent neurological sequelae. Viral encephalitis and multiple sclerosis are examples of important human diseases in which the pathogenic contribution of monocytes recruited from the bone marrow plays a critical role in the clinical expression of disease, as they differentiate into macrophage or dendritic cells in the CNS to carry out effector functions. While antigen-specific lymphocyte populations are central to the adaptive immune response in both cases, in viral encephalitis a prominent macrophage infiltration may mediate immunopathological damage, seizure induction, and death. However, the autoimmune response to non-replicating, non-infectious, but abundant, self antigen has a different disease progression, associated with differentiation of significant numbers of infiltrating monocytes into dendritic cells in the CNS. Whilst a predominant presence of macrophages or dendritic cells in the inflamed CNS in viral encephalitis or multiple sclerosis is well described, the way in which the inflamed CNS mobilizes monocytes in the bone marrow to migrate to the CNS and the key drivers that lead to these specific differentiation pathways in vivo are not well understood. Here we review the current understanding of factors facilitating inflammatory monocyte generation, migration and entry into the brain, as well as their differentiation towards macrophages or dendritic cells in viral and autoimmune disease in relation to their respective disease outcomes.

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Section: Monocyte Differentiation In Steady Statementioning

confidence: 99%

Section: Monocyte Differentiation In Steady Statementioning

confidence: 99%

Section: Inflammatory Signals and Monocyte Differentiationmentioning

confidence: 99%

Section: Effect Of Resident Cells On Monocyte Differentiationmentioning

confidence: 99%

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The plasticity of inflammatory monocyte responses to the inflamed central nervous system

Ashhurst

Vreden

Niewold

et al. 2014

Cellular Immunology

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“…The GM-CSF enhances neutrophil phagocytosis, enhances release of chemotactic factors by neutrophils, 30 induces production of the pro-inflammatory cytokines by macrophages and increases their function as antigen-presenting cells, 31 and in this way promotes acute inflammatory reactions. In the presence of IL-4, GM-CSF can initiate a specific differentiation of monocytes into osteoclast-like multinucleated giant cells 32 that create a background for chronic inflammation. GM-CSF can also contribute to allergic inflammation by promoting growth, prolonged survival and activation of eosinophils and basophils.…”

Section: Introductionmentioning

confidence: 99%

The immunoregulatory and allergy‐associated cytokines in the aetiology of the otitis media with effusion

Smirnova

Birchall

Pearson

2004

Mediators of Inflammation

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Inflammation in the middle ear mucosa, which can be provoked by different primary factors such as bacterial and viral infection, local allergic reactions and reflux, is the crucial event in the pathogenesis of otitis media with effusion (OME). Unresolved acute inflammatory responses or defective immunoregulation of middle inflammation can promote chronic inflammatory processes and stimulate the chronic condition of OME. Cytokines are the central molecular regulators of middle ear inflammation and can switch the acute phase of inflammation in the chronic stage and induce molecular-pathological processes leading to the histopathological changes accompanying OME. In this review we present cytokines identified in otitis media, immunoregulatory [interleukin (IL)-2, IL-10, transforming growth factor-beta]) and allergy associated (IL-4, IL-5, granulocyte-macrophage colony-stimulating factor), as crucial molecular regulators, responsible for chronic inflammation in the middle ear and the chronic condition of OME.

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IL-4, but not vitamin D3, induces monoblastic cell line UG3 to differentiate into multinucleated giant cells on osteoclast lineage

Kaji

Ikeda

et al. 2000

J. Cell. Physiol.

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The formation of multinucleated giant cells (MGCs) from monocytes/macrophages is controlled by various cytokines, the roles of which are not fully understood. Both interleukin (IL)-4 and 1alpha,25(OH)(2) vitamin D(3) (D(3)) are known to induce MGC formation from monocytes/macrophages. D(3) is also known as a stimulator of osteoclast formation in the presence of stroma cells, and IL-4 as an inhibitor. Previously, we showed that IL-4-induced MGCs from monocytes/macrophages expressed tartrate resistant acid phosphatase (TRAP) activity and hydroxyapatite-resorptive activity in the presence of M-CSF without stroma cells. In this study, we examined the effects of D(3) and/or IL-4 on MGC formation and the characteristics of these MGCs using a monoblastic cell line (UG3), to elucidate the involvement of these factors in osteoclast development without stroma cells. D(3)-induced MGCs showed none of the markers of osteoclasts, such as TRAP activity, calcitonin receptor (cal-R) expression, hydroxyapatite-resorptive activity, and bone-resorptive activity. A low concentration of D(3) synergistically stimulated IL-4-induced TRAP-positive MGC formation, whereas a high concentration of D(3) inhibited it. When IL-4 was added on day 7 of the 2-week culture with D(3), TRAP positivity reached maximum. On the other hand, delayed addition of D(3) on day 7 of culture did not increase the TRAP positivity. Although the fusion rate increased during the first week of the 2-week culture in the presence of D(3), it increased further in the second week following the addition of IL-4 on day 7. Furthermore, IL-4-induced, or IL-4- and D(3)-induced MGCs differentiated into functional osteoclasts with bone-resorptive activity following coculture with osteoblastic cells, whereas D(3)-induced MGCs did not acquire bone-resorptive activity even after coculture with osteoblastic cells in the presence of D(3). These findings suggest that IL-4 initiates osteoclast development of UG3 cells, although stroma cells were necessary for development of functional osteoclasts. On the other hand, D(3) had only a "supportive" effect on this differentiation. IL-4 and direct contact with stroma cells may regulate different stages in the multistep process of osteoclastogenesis of UG3 cells.

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Generation of CD1+RelB+ dendritic cells and tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated giant cells from human monocytes

Cited by 191 publications

References 37 publications

The plasticity of inflammatory monocyte responses to the inflamed central nervous system

The plasticity of inflammatory monocyte responses to the inflamed central nervous system

The immunoregulatory and allergy‐associated cytokines in the aetiology of the otitis media with effusion

IL-4, but not vitamin D3, induces monoblastic cell line UG3 to differentiate into multinucleated giant cells on osteoclast lineage

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