The interplay between surfaces and soluble factors define the immunologic and angiogenic properties of myeloid dendritic cells

Sprague, Leslee; Muccioli, Maria; Pate, Michelle; Meles, Evan; McGinty, John W.; Nandigam, Harika; Venkatesh, Amritha; Gu, Mingyu; Mansfield, Kristen; Rutowski, Andrew; Omosebi, Omowaleola; Courrèges, Marı́a C.; Benencia, Fabián

doi:10.1186/1471-2172-12-35

Cited by 26 publications

(25 citation statements)

References 70 publications

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“…The same might apply to studies with ECMp in a murine system, where bovine collagen I and vitronectin influenced the maturation of murine blood monocytederived iDC and caused higher IL-12p40 release, T cell activation, and proliferation. 44 However, it has also been reported, that murine bone marrow-derived DC were completely unresponsive to maturation stimuli after initial culture on collagen I, 25 which is consistent with our results. Whether the lack of iDC maturation demonstrated for all ECMp tested in our study will also result in reduced T cell proliferation within a mixed lymphocyte culture is not clear.…”

supporting

confidence: 83%

“…24 Other groups demonstrated the influence of ECMp coating of biomaterials on the properties of mature DC. [25][26][27] Other APC types, such as B cells, 28,29 might be affected by the adjuvant activity of ECMp or even modulate the maturation and functions of DC. 30 Experimental data in the murine system demonstrated that ECMp could influence the differentiation, proliferation, or cytokine secretion pattern of B-1b cells.…”

mentioning

confidence: 99%

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Absence of Immune Responses with Xenogeneic Collagen and Elastin

Bayrak

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et al. 2013

Tissue Engineering Part A

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Novel tissue-engineering approaches for cardiovascular matrices based on xenogeneic extracellular matrix protein (ECMp) constituents require a detailed evaluation of their interaction with essential immune cell subsets playing a role in innate or adaptive immunity. Therefore, in this study, the effects of xenogeneic (porcine, bovine) collagen type I and elastin as the two main components of the heart valve ECM were analyzed in comparison to their human equivalents. First, their potential to induce maturation and cytokine secretion of human dendritic cells (DC) was tested by flow cytometry. Second, the influence on proliferation and cytokine release of purified human B and T cells was measured. We could demonstrate that xenogeneic collagen type I and elastin are not able to trigger the maturation of DC as verified by the lack of CD83 induction accompanied by a low tumor necrosis factor-a release. Moreover, both ECMp showed no effect on the proliferation and the interleukin-6 release of either unstimulated or prestimulated B cells. Additionally, anti-CD3-induced purified T cell proliferation and secretion of cytokines was not affected. All in vitro data verify the low immunogenicity of porcine and bovine collagen type I and elastin and favor their suitability for tissue-engineered scaffolds.

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supporting

confidence: 83%

mentioning

confidence: 99%

Absence of Immune Responses with Xenogeneic Collagen and Elastin

Bayrak

Prüger

Stock

et al. 2013

Tissue Engineering Part A

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“…Historically, intercellular communication mechanisms responsible for mediating immune responses have focused on cell-to-cell and receptor–ligand mediated interactions (41) as well as soluble cytokines, chemokines, and angiogenic factors (42). Recently, EVs have emerged as novel mediators of intercellular communication composed of both exosome (30–100 nm) and microvesicle (100 nm–1 μm) subpopulations.…”

Section: Discussionmentioning

confidence: 99%

Human Melanoma-Derived Extracellular Vesicles Regulate Dendritic Cell Maturation

et al. 2017

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Evolution of melanoma from a primary tumor to widespread metastasis is crucially dependent on lymphatic spread. The mechanisms regulating the initial step in metastatic dissemination via regional lymph nodes remain largely unknown; however, evidence supporting the establishment of a pre-metastatic niche is evolving. We have previously described a dysfunctional immune profile including reduced expression of dendritic cell (DC) maturation markers in the first node draining from the primary tumor, the sentinel lymph node (SLN). Importantly, this phenotype is present prior to evidence of nodal metastasis. Herein, we evaluate melanoma-derived extracellular vesicles (EVs) as potential mediators of the premetastatic niche through cargo-specific polarization of DCs. DCs matured in vitro in the presence of melanoma EVs demonstrated significantly impaired expression of CD83 and CD86 as well as decreased expression of Th1 polarizing chemokines Flt3L and IL15 and migration chemokines MIP-1α and MIP-1β compared to liposome-treated DCs. Profiling of melanoma EV cargo identified shared proteomic and RNA signatures including S100A8 and S100A9 protein cargo, which in vitro compromised DC maturation similar to melanoma EVs. Early evidence demonstrates that similar EVs can be isolated from human afferent lymphatic fluid ex vivo. Taken together, here, we propose melanoma EV cargo as a mechanism by which DC maturation is compromised warranting further study to consider this as a potential mechanism enabled by the primary tumor to establish the premetastatic niche in tumor-draining SLNs of patients.

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“…We have previously reported that these cells exhibit high plasticity, being capable of acquiring angiogenic properties in vivo under pathological conditions (15). We hypothesized that this might be caused not only by the presence of specific cytokines or growth factors, but also by the interaction with different extracellular matrix (ECM) components as we have recently demonstrated (40). Taking into account this, we decided to determine the relevance of substrate adherence on the biology of myeloid(m) DCs.…”

Section: Resultsmentioning

confidence: 99%

Adhesion to substrates induces dendritic cell endothelization and decreases immunological response

et al. 2013

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Dendritic cells (DCs) are antigen presenting cells capable of inducing specific immune responses against microbial infections, transplant antigens, or tumors. DCs have been shown to possess a high plasticity showing different phenotypes in response to their microenvironment. For example, tumor-associated DCs can acquire an angiogenic phenotype thus promoting tumor growth. Further, DCs cultured in vitro under different conditions are able to upregulate the expression of endothelial markers and to express angiogenic factors. Indeed, it has been shown that soluble factors such as VEGF of PGE-2, that are present in the microenvironment of several tumors, affect the biology of these cells. We hypothesize that in addition to soluble factors the adhesion to different substrates will also define the phenotype and function of DCs. Herewith we demonstrate that murine myeloid(m) DCs upregulate endothelial markers such as VE-Cadherin, and to a lesser extent TIE-2, and decrease their immune capabilities when cultured on solid surfaces as compared with the same cells cultured on ultra-low binding (ULB) surfaces. On the other hand, the expression of angiogenic molecules at the level of RNA was not different among these cultures. In order to further investigate this phenomenon we used the murine ID8 model of ovarian cancer which can generate solid tumors when cancer cells are injected subcutaneously or a malignant ascites when they are injected intraperitoneally. This model gave us the unique opportunity to investigate DCs in suspension or attached to solid surfaces under the influence of the same tumor cells. We were able to determine that DCs present in solid tumors showed higher levels of expression of endothelial markers and angiogenic molecules but were not able to respond to inflammatory stimuli at the same extent as DCs recovered from ascites. Moreover, mDCs cultured on ULB surfaces in the presence of tumor factors do not expressed endothelial markers. Taking into account all these data we consider that tumor factors might be responsible for inducing angiogenic properties in DCs, but that in some settings the expression of endothelial markers such as VE-Cadherin and TIE-2 might be a function of attachment to solid surfaces and independent of the angiogenic properties of these cells.

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The interplay between surfaces and soluble factors define the immunologic and angiogenic properties of myeloid dendritic cells

Cited by 26 publications

References 70 publications

Absence of Immune Responses with Xenogeneic Collagen and Elastin

Absence of Immune Responses with Xenogeneic Collagen and Elastin

Human Melanoma-Derived Extracellular Vesicles Regulate Dendritic Cell Maturation

Adhesion to substrates induces dendritic cell endothelization and decreases immunological response

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