TNF Skews Monocyte Differentiation from Macrophages to Dendritic Cells

Chomarat, Pascale; Dantin, Carole; Bennett, Lynda; Banchereau, Jacques; Palucka, A. Karolina

doi:10.4049/jimmunol.171.5.2262

Cited by 170 publications

(142 citation statements)

References 41 publications

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“…C1q, a recognition unit of complement, is mainly considered as a pro-inflammatory mediator, sharing several features with TNF-a and CD40L which are pivotal DC-activating factors [9,11,27,29]. However, we found that C1qDC did not express the chemokine receptor CCR-7, usually up-regulated in mature DC (Fig.…”

Section: Generation Of Dc-signcontrasting

confidence: 41%

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Immune modulation of human dendritic cells by complement

et al. 2007

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Deficiency in complement proteins such as C1q is associated with the development of systemic lupus erythematosus (SLE). Here, we show that the differentiation of dendritic cells (DC) in the presence of C1q (C1qDC) gives rise to CD1a + /DC-SIGN + cells with high phagocytic capacity and low expression of CD80, CD83 and CD86. Further, when C1qDC were exposed to LPS, a significant reduction in the production of IL-6, TNF-a and IL-10 occurred with a limited up-regulation of CD80, CD83 and CD86. In addition, C1qDC were less responsive to activation by CD40L in terms of IL-12p70 secretion and CD86 expression. C1qDC showed an impaired ability to stimulate alloreactive T cells, with a reduced production of IFN-c. In conclusion, we have shown that C1q is a potent modulator of DC, resulting in cells characterized by an impaired capacity of cytokine production and an impaired up-regulation of costimulatory molecules, leading to a limited T cell response. Therefore, we hypothesize that, next to a pivotal role in the safe clearance of apoptotic cells, C1q regulates the threshold of DC activation and thereby prevents hyperactivation of the overall immune response.

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Section: Generation Of Dc-signcontrasting

confidence: 41%

“…Although DC developed more dendrites than C1qDC (Fig. 1A), both cell populations exhibited a condensed cytoplasm, typical of DC, and an absence of cells with vacuolated cytoplasm, excluding a differentiation towards macrophages [27].…”

Section: Generation Of Dc-signmentioning

confidence: 99%

Immune modulation of human dendritic cells by complement

et al. 2007

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“…However, the abnormal cytokine profile that has been shown for NOD macrophages (38) might make them inhibitory instead of supportive for the growth and maturation of DC in culture. A potential inhibitory cytokine might be IL-6 as it has been shown that IL-6 shifts the differentiation of human monocytes from DC toward macrophages, whereas TNF-␣ favors maturation into DC (39,40); however, in the supernatants collected from day 7 BM cultures, we could not detect appreciable levels of TNF-␣, IL-6, or IL-1␤, and when stimulated with LPS, C57BL and NOD BM-derived cells produced similar levels of these cytokines (data not shown). Therefore, it is less likely that an increased production of inhibitory cytokines in NOD cultures is the decisive factor in the deviated DC generation.…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow Precursors of Nonobese Diabetic Mice Develop into Defective Macrophage-Like Dendritic Cells In Vitro

Nikolić

Bunk

Drexhage

et al. 2004

The Journal of Immunology

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The NOD mouse spontaneously develops autoimmune diabetes. Dendritic cells (DC) play a crucial role in the autoimmune response. Previous studies have reported a defective DC generation in vitro from the NOD mouse bone marrow (BM), but a deviated development of myeloid precursors into non-DC in response to GM-CSF was not considered. In this study, we demonstrate several abnormalities during myeloid differentiation of NOD BM precursors using GM-CSF in vitro. 1) We found reduced proliferation and increased cell death in NOD cultures, which explain the previously reported low yield of DC progeny in NOD. Cell yield in NOR cultures was normal. 2) In a detailed analysis GM-CSF-stimulated cultures, we observed in both NOD and NOR mice an increased frequency of macrophages, identified as CD11c+/MHCII− cells with typical macrophage morphology, phenotype, and acid phosphatase activity. This points to a preferential maturation of BM precursors into macrophages in mice with the NOD background. 3) The few CD11c+/MHCIIhigh cells that we obtained from NOD and NOR cultures, which resembled prototypic mature DC, appeared to be defective in stimulating allogeneic T cells. These DC had also strong acid phosphatase activity and elevated expression of monocyte/macrophage markers. In conclusion, in this study we describe a deviated development of myeloid BM precursors of NOD and NOR mice into macrophages and macrophage-like DC in vitro. Potentially, these anomalies contribute to the dysfunctional regulation of tolerance in NOD mice yet are insufficient to induce autoimmune diabetes because they occurred partly in NOR mice.

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“…M-CSF signaling in monocytes (30). We therefore analyze TNF-a in DC differentiating cultures and observe that Wnt proteins also promoted TNF-a secretion, which may redirect DC differentiation (Fig.…”

Section: Wnt Signaling Induces the Secretion Of Il-6 Il-10 And Tnf-mentioning

confidence: 99%

Wnt5a Skews Dendritic Cell Differentiation to an Unconventional Phenotype with Tolerogenic Features

Valencia

Hernández-López

Martínez

et al. 2011

The Journal of Immunology

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Dendritic cells (DCs) are critical regulators of immune responses that integrate signals from the innate and adaptive immune system and orchestrate T cell responses toward either immunity or tolerance. Growing evidence points to the Wnt signaling pathway as a pivotal piece in the immune balance and focuses on DCs as a direct target for their immunoregulatory role. Our results show that the increase in Wnt5a signaling during the differentiation of human DCs from monocytes alters their phenotype and compromises their subsequent capacity to mature in response to TLR-dependent stimuli. These Wnt5a-DCs produce scant amounts of IL-12p70 and TNF-α but increased levels of IL-10. Consequently, these Wnt5a-DCs have a reduced capacity to induce Th1 responses that promote IL-10 secretion by CD4 T cells. Changes in the transcriptional profile of Wnt5a-DCs correlate with their unconventional phenotype caused presumably by increased IL-6/IL-10 signaling during the process of DC differentiation. The effect of Wnt5a is not a consequence of β-catenin accumulation but is dependent on noncanonical Ca2+/calmodulin-dependent protein kinase II/NF-κB signaling. Our results therefore suggest that under high levels of Wnt5a, typical of the inflammatory state and sepsis, monocytes could differentiate into unconventional DCs with tolerogenic features.

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TNF Skews Monocyte Differentiation from Macrophages to Dendritic Cells

Cited by 170 publications

References 41 publications

Immune modulation of human dendritic cells by complement

Immune modulation of human dendritic cells by complement

Bone Marrow Precursors of Nonobese Diabetic Mice Develop into Defective Macrophage-Like Dendritic Cells In Vitro

Wnt5a Skews Dendritic Cell Differentiation to an Unconventional Phenotype with Tolerogenic Features

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