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Frontiers in Immunology 2018Dendritic cells (DCs) are key antigen-presenting cells that control the induction of both tolerance and immunity. Understanding the molecular mechanisms regulating DCs... (Review)
Review
Dendritic cells (DCs) are key antigen-presenting cells that control the induction of both tolerance and immunity. Understanding the molecular mechanisms regulating DCs commitment toward a regulatory- or effector-inducing profile is critical for better designing prophylactic and therapeutic approaches. Initially identified in dexamethasone-treated thymocytes, the glucocorticoid-induced leucine zipper (GILZ) protein has emerged as a critical factor mediating most, but not all, glucocorticoids effects in both non-immune and immune cells. This intracellular protein exerts pleiotropic effects through interactions with transcription factors and signaling proteins, thus modulating signal transduction and gene expression. GILZ has been reported to control the proliferation, survival, and differentiation of lymphocytes, while its expression confers anti-inflammatory phenotype to monocytes and macrophages. In the past twelve years, a growing set of data has also established that GILZ expression in DCs is a molecular switch controlling their T-cell-priming capacity. Here, after a brief presentation of GILZ isoforms and functions, we summarize current knowledge regarding GILZ expression and regulation in DCs, in both health and disease. We further present the functional consequences of GILZ expression on DCs capacity to prime effector or regulatory T-cell responses and highlight recent findings pointing to a broader role of GILZ in the fine tuning of antigen capture, processing, and presentation by DCs. Finally, we discuss future prospects regarding the possible roles for GILZ in the control of DCs function in the steady state and in the context of infections and chronic pathologies.
Topics: Animals; Antigen Presentation; Antigens; Biomarkers; Dendritic Cells; Gene Expression Regulation; Glucocorticoids; Humans; Immune Tolerance; Immunomodulation; Leucine Zippers
PubMed: 29915587
DOI: 10.3389/fimmu.2018.01232 -
Cellular & Molecular Immunology Jun 2006Dendritic cells (DCs) are the most potent professional antigen-presenting cells, and capable of stimulating naïve T cells and driving primary immune responses. DCs are... (Review)
Review
Dendritic cells (DCs) are the most potent professional antigen-presenting cells, and capable of stimulating naïve T cells and driving primary immune responses. DCs are poised to capture antigen, migrate to draining lymphoid organs, and after a process of maturation, select antigen-specific lymphocytes to which they present the processed antigen, thereby inducing immune responses. The development of protocols for the ex vivo generation of DCs may provide a rationale for designing and developing DC-based vaccination for the treatment of tumors. There are now several strategies being applied to upload antigens to DCs and manipulate DC vaccines. DC vaccines are able to induce therapeutic and protective antitumor immunity. Numerous studies indicated that hepatocellular carcinoma (HCC) immunotherapies utilizing DC-presenting tumor-associated antigens could stimulate an antitumour T cell response leading to clinical benefit without any significant toxicity. DC-based tumor vaccines have become a novel immunoadjuvant therapy for HCC.
Topics: Animals; Antigen Presentation; Antigens, Neoplasm; Carcinoma, Hepatocellular; Dendritic Cells; Humans; Immunotherapy; Liver Neoplasms
PubMed: 16893500
DOI: No ID Found -
Journal of Biomedicine & Biotechnology 2011Gastric cancer (GC) is the fourth most common cancer and the second most frequent cause of cancer-related deaths, accounting for 10.4% of cancer deaths worldwide.... (Review)
Review
Gastric cancer (GC) is the fourth most common cancer and the second most frequent cause of cancer-related deaths, accounting for 10.4% of cancer deaths worldwide. Despite the improvements, estimated cure rates for patients with advanced stages remain poor, and in the metastatic setting, chemotherapy is the mainstay of palliative therapy and results in objective response rates (ORRs) of only 20-40% and median overall survivals (OS) of 8-10 months. Therefore, many investigators believe that the potential for making significant progress lies in understanding and exploiting the molecular biology of these tumors to investigate new therapeutic strategies to combat GC, such as specific immunotherapy. In this paper, we analyze the different approaches used for immune-based (especially dendritic and T cells) therapies to gastric cancer treatment and discuss the results obtained in preclinical models as in clinical trials.
Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigen-Presenting Cells; Carcinoma, Squamous Cell; Dendritic Cells; Humans; Immunotherapy; Killer Cells, Natural; Molecular Targeted Therapy; Stomach Neoplasms; Vascular Endothelial Growth Factor A
PubMed: 22253528
DOI: 10.1155/2011/437348 -
Cellular and Molecular Life Sciences :... Mar 2017Dendritic cells (DC) play a pivotal role in the tumor microenvironment (TME). As the primary antigen-presenting cells in the tumor, DCs modulate anti-tumor responses by... (Review)
Review
Dendritic cells (DC) play a pivotal role in the tumor microenvironment (TME). As the primary antigen-presenting cells in the tumor, DCs modulate anti-tumor responses by regulating the magnitude and duration of infiltrating cytotoxic T lymphocyte responses. Unfortunately, due to the immunosuppressive nature of the TME, as well as the inherent plasticity of DCs, tumor DCs are often dysfunctional, a phenomenon that contributes to immune evasion. Recent progresses in our understanding of tumor DC biology have revealed potential molecular targets that allow us to improve tumor DC immunogenicity and cancer immunotherapy. Here, we review the molecular mechanisms that drive tumor DC dysfunction. We discuss recent advances in our understanding of tumor DC ontogeny, tumor DC subset heterogeneity, and factors in the tumor microenvironment that affect DC recruitment, differentiation, and function. Finally, we describe potential strategies to optimize tumor DC function in the context of cancer therapy.
Topics: Animals; Dendritic Cells; Humans; Immunity; Models, Biological; Neoplasms
PubMed: 27491428
DOI: 10.1007/s00018-016-2317-8 -
Clinical and Experimental Immunology Jul 1996Since Aschoff's reticuloendothelial system was abandoned a few decades ago, classification and characterization of the mononuclear phagocyte and dendritic cell systems... (Comparative Study)
Comparative Study Review
Since Aschoff's reticuloendothelial system was abandoned a few decades ago, classification and characterization of the mononuclear phagocyte and dendritic cell systems have evolved separately or even in competition with one another. New information has now become available indicating that monocytes/macrophages and dendritic cells have a common origin in the bone marrow, and may even transdifferentiate. Morphological and functional distinctions-although valid under certain conditions-have been blurred by revelation of the versatility of monocytes/macrophages and dendritic cells in response to different contextual needs in inflammation and immunity. Monocytes/macrophages and dendritic cells share a sentinel, receptor/effector, and presentation mode, and may either activate or silence specific immune reactions. In keeping with the view of monocytes/macrophages and dendritic cells as interactive sentinels, we suggest that the mono-nuclear phagocyte and dendritic cell systems be replaced by the custocyte system (custos, Lat = sentinel, guard) as a unifying concept. Within the custocyte system, we recognize type I, type II, and type III custocytes. Type I and II custocytes exhibit predominance of presentation or effector/presenter interdependency, respectively, while type III custocytes are bipolar, passing through type I- and type II-like phases during their development and in inflammatory responses. The custocyte system brings into view monocytes/macrophages and dendritic cells as dynamic players in immunity and inflammation with a high degree of derivational, phenotypic, functional, and molecular plasticity.
Topics: Animals; Cell Differentiation; Dendritic Cells; Humans; Phagocytes
PubMed: 8697614
DOI: 10.1046/j.1365-2249.1996.d01-740.x -
Frontiers in Immunology 2021Dendritic cells (DC) are central to regulating innate and adaptive immune responses. Strategies that modify DC function provide new therapeutic opportunities in... (Comparative Study)
Comparative Study
Dendritic cells (DC) are central to regulating innate and adaptive immune responses. Strategies that modify DC function provide new therapeutic opportunities in autoimmune diseases and transplantation. Current pharmacological approaches can alter DC phenotype to induce tolerogenic DC (tolDC), a maturation-resistant DC subset capable of directing a regulatory immune response that are being explored in current clinical trials. The classical phenotypic characterization of tolDC is limited to cell-surface marker expression and anti-inflammatory cytokine production, although these are not specific. TolDC may be better defined using gene signatures, but there is no consensus definition regarding genotypic markers. We address this shortcoming by analyzing available transcriptomic data to yield an independent set of differentially expressed genes that characterize human tolDC. We validate this transcriptomic signature and also explore gene differences according to the method of tolDC generation. As well as establishing a novel characterization of tolDC, we interrogated its translational utility , demonstrating this geneset was enriched in the liver, a known tolerogenic organ. Our gene signature will potentially provide greater understanding regarding transcriptional regulators of tolerance and allow researchers to standardize identification of tolDC used for cellular therapy in clinical trials.
Topics: Databases, Genetic; Dendritic Cells; Gene Expression Profiling; Humans; Immune Tolerance; Lipopolysaccharides; Phenotype; Predictive Value of Tests; Reproducibility of Results; Transcriptome
PubMed: 34745103
DOI: 10.3389/fimmu.2021.733231 -
Frontiers in Immunology 2020Over a half century, organ transplantation has become an effective method for the treatment of end-stage visceral diseases. Although the application of... (Review)
Review
Over a half century, organ transplantation has become an effective method for the treatment of end-stage visceral diseases. Although the application of immunosuppressants (IS) minimizes the rate of allograft rejection, the common use of IS bring many adverse effects to transplant patients. Moreover, true transplant tolerance is very rare in clinical practice. Dendritic cells (DCs) are thought to be the most potent antigen-presenting cells, which makes a bridge between innate and adaptive immunity. Among their subsets, a small portion of DCs with immunoregulatory function was known as tolerogenic DC (Tol-DC). Previous reports demonstrated the ability of adoptively transferred Tol-DC to approach transplant tolerance in animal models. In this study, we summarized the properties, ex vivo generation, metabolism, and clinical attempts of Tol-DC. Tol-DC is expected to become a substitute for IS to enable patients to achieve immune tolerance in the future.
Topics: Animals; Dendritic Cells; Graft Rejection; Graft Survival; Humans; Immunotherapy; Organ Transplantation; Transplantation Tolerance
PubMed: 33123131
DOI: 10.3389/fimmu.2020.552988 -
International Journal of Molecular... Jan 2023Dendritic cell (DC) vaccines are a type of immunotherapy that relies on the communication of DCs with other aspects of the immune system. DCs are potent...
Dendritic cell (DC) vaccines are a type of immunotherapy that relies on the communication of DCs with other aspects of the immune system. DCs are potent antigen-presenting cells involved in the activation of innate immune responses and education of adaptive immunity, making them ideal targets for immunotherapies. Innate lymphoid cells (ILCs) are relatively newly identified in the field of immunology and have important roles in health and disease. The studies described here explored the communications between type 3 ILCs (ILC3s) and DCs using a murine model of DC-based vaccination. Local and systemic changes in ILC3 populations following the administration of a DC vaccine were observed, and upon challenge with B16F10 melanoma cells, changes in ILC3 populations in the lungs were observed. The interactions between DCs and ILC3s should be further explored to determine the potential that their communications could have in health, disease, and the development of immunotherapies.
Topics: Animals; Mice; Lymphocytes; Immunity, Innate; Dendritic Cells; Adaptive Immunity; Vaccines
PubMed: 36768726
DOI: 10.3390/ijms24032403 -
Frontiers in Immunology 2023Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell... (Review)
Review
Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell population to capture, process and present antigens to activate naïve T cells and originate favorable immune responses in many diseases, such as cancer. However, in the last decades, it has been observed that DCs not only promote beneficial responses, but also drive the initiation and progression of some pathologies, including inflammatory bowel disease (IBD). In line with those notions, different therapeutic approaches have been tested to enhance or impair the concentration and role of the different DC subsets. The blockade of inhibitory pathways to promote DCs or DC-based vaccines have been successfully assessed in cancer, whereas the targeting of DCs to inhibit their functionality has proved to be favorable in IBD. In this review, we (a) described the general role of DCs, (b) explained the DC subsets and their role in immunogenicity, (c) analyzed the role of DCs in cancer and therapeutic approaches to promote immunogenic DCs and (d) analyzed the role of DCs in IBD and therapeutic approaches to reduced DC-induced inflammation. Therefore, we aimed to highlight the "yin-yang" role of DCs to improve the understand of this type of cells in disease progression.
Topics: Humans; Dendritic Cells; Adaptive Immunity; Neoplasms; Inflammatory Bowel Diseases; Disease Progression
PubMed: 38239364
DOI: 10.3389/fimmu.2023.1321051 -
Frontiers in Endocrinology 2020Nutrients are required for growth and survival of all cells, but are also crucially involved in cell fate determination of many cell types, including immune cells. There... (Review)
Review
Nutrients are required for growth and survival of all cells, but are also crucially involved in cell fate determination of many cell types, including immune cells. There is a growing appreciation that the metabolic micro-environment also plays a major role in shaping the functional properties of dendritic cells (DCs). Under pathological conditions nutrient availability can range from a very restricted supply, such as seen in a tumor micro-environment, to an overabundance of nutrients found in for example obese adipose tissue. In this review we will discuss what is currently known about the metabolic requirements for DC differentiation and immunogenicity and compare that to how function and fate of DCs under pathological conditions can be affected by alterations in environmental levels of carbohydrates, lipids and amino acids as well as by other metabolic cues, including availability of oxygen, redox homeostasis and lactate levels. Many of these insights have been generated using model systems, which have revealed highly diverse effects of different metabolic cues on DC function. However, they also stress the importance of shifting toward more physiologically relevant experimental settings to be able to fully delineate the role of the metabolic surroundings in its full complexity in shaping the functional properties of DCs in health and disease.
Topics: Animals; Cell Differentiation; Dendritic Cells; Energy Metabolism; Humans
PubMed: 33013685
DOI: 10.3389/fendo.2020.00555