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Frontiers in Immunology 2021Platelet transfusions are a frequently administered therapy for especially hemato-oncological patients with thrombocytopenia. Next to their primary function in...
Platelet transfusions are a frequently administered therapy for especially hemato-oncological patients with thrombocytopenia. Next to their primary function in hemostasis, currently there is increased attention for the capacity of platelets to affect the function of various cells of the immune system. Here, we investigate the capacity of platelets to immuno-modulate monocyte-derived dendritic cells (moDC) as well as primary dendritic cells and effects on subsequent T cell responses. Platelets significantly inhibited pro-inflammatory (IL-12, IL-6, TNFα) and increased anti-inflammatory (IL-10) cytokine production of moDCs primed with toll-like receptor (TLR)-dependent and TLR-independent stimuli. Transwell assays and ultracentrifugation revealed that a soluble factor secreted by platelets, but not microvesicles, inhibited DC activation. Interestingly, platelet-derived soluble mediators also inhibited cytokine production by human stimulated myeloid CD1c+ conventional DC2. Moreover, platelets and platelet-derived soluble mediators inhibited T cell priming and T helper differentiation toward an IFN+ Th1 phenotype by moDCs. Overall, these results show that platelets are able to inhibit the pro-inflammatory properties of DCs, and may even induce an anti-inflammatory DC phenotype, with decreased T cell priming capacity by the DC. The results of this study provide more insight in the potential role of platelets in immune modulation, especially in the context of platelet transfusions.
Topics: Blood Platelets; Cell Culture Techniques; Cell Differentiation; Culture Media; Cytokines; Dendritic Cells; Humans; Lymphocyte Activation; Secretory Pathway; T-Lymphocytes
PubMed: 33737933
DOI: 10.3389/fimmu.2021.631285 -
Frontiers in Immunology 2021Dendritic cells (DCs) play essential roles in innate and adaptive immunity and show high heterogeneity and intricate ontogeny. Advances in high-throughput sequencing... (Review)
Review
Dendritic cells (DCs) play essential roles in innate and adaptive immunity and show high heterogeneity and intricate ontogeny. Advances in high-throughput sequencing technologies, particularly single-cell RNA sequencing (scRNA-seq), have improved the understanding of DC subsets. In this review, we discuss in detail the remarkable perspectives in DC reclassification and ontogeny as revealed by scRNA-seq. Moreover, the heterogeneity and multifunction of DCs during diseases as determined by scRNA-seq are described. Finally, we provide insights into the challenges and future trends in scRNA-seq technologies and DC research.
Topics: Cell Lineage; Dendritic Cells; Humans; Lymphocytes, Tumor-Infiltrating; Neoplasms; Sequence Analysis, RNA; Single-Cell Analysis; Tumor Microenvironment
PubMed: 34566965
DOI: 10.3389/fimmu.2021.711329 -
Molecular Immunology Apr 2020Dendritic cells (DCs) orchestrate adaptive immune responses. In healthy individuals, DCs are drivers and fine-tuners of T cell responses directed against invading... (Review)
Review
Dendritic cells (DCs) orchestrate adaptive immune responses. In healthy individuals, DCs are drivers and fine-tuners of T cell responses directed against invading pathogens or cancer cells. In parallel, DCs control autoreactive T cells, thereby maintaining T cell tolerance. Under various disease conditions, a disruption of this delicate balance can lead to chronic infections, tumor evasion, or autoimmunity. While great efforts have been made to unravel the origin and development of this powerful cell type in mice, only little is known about the ontogeny of human DCs. Here, we summarize the current understanding of the developmental path of DCs from hematopoietic stem cells to fully functional DCs in their local tissue environment and provide a template for the identification of DCs across various tissues.
Topics: Animals; Autoimmunity; Cell Differentiation; Cellular Microenvironment; Dendritic Cells; Hematopoietic Stem Cells; Humans; Immune Tolerance; Mice; Models, Immunological; Organ Specificity; Phenotype
PubMed: 32114182
DOI: 10.1016/j.molimm.2020.02.010 -
International Journal of Molecular... Oct 2020Liver fibrosis is a chronic, highly prevalent disease that may progress to cirrhosis and substantially increases the risk for development of hepatocellular carcinoma... (Review)
Review
Liver fibrosis is a chronic, highly prevalent disease that may progress to cirrhosis and substantially increases the risk for development of hepatocellular carcinoma (HCC). Fibrotic livers are characterized by an inflammatory microenvironment that is composed of various immunologically active cells, including liver-resident populations (e.g., Kupffer cells, hepatic stellate cells and sinusoidal endothelium) and infiltrating leukocytes (e.g., monocytes, monocyte-derived macrophages, neutrophils and lymphocytes). While inflammatory injury drives both fibrogenesis and carcinogenesis, the tolerogenic microenvironment of the liver conveys immunosuppressive effects that encourage tumor growth. An insufficient crosstalk between dendritic cells (DCs), the professional antigen presenting cells, and T cells, the efficient anti-tumor effector cells, is one of the main mechanisms of HCC tumor tolerance. The meticulous analysis of patient samples and mouse models of fibrosis-HCC provided in-depth insights into molecular mechanisms of immune interactions in liver cancer. The therapeutic modulation of this multifaceted immunological response, e.g., by inhibiting immune checkpoint molecules, in situ vaccination, oncolytic viruses or combinations thereof, is a rapidly evolving field that holds the potential to improve the outcome of patients with HCC. This review aims to highlight the current understanding of DC-T cell interactions in fibrogenesis and hepatocarcinogenesis and to illustrate the potentials and pitfalls of therapeutic clinical translation.
Topics: Animals; Carcinogenesis; Carcinoma, Hepatocellular; Cell Communication; Dendritic Cells; Humans; Immune Tolerance; Inflammation; Liver Cirrhosis; Liver Neoplasms; T-Lymphocytes
PubMed: 33036244
DOI: 10.3390/ijms21197378 -
Immunological Investigations Nov 2022As the most potent professional antigen presenting cells, dendritic cells (DCs) have the ability to activate both naive CD4 and CD8 T cells. Recognized for their... (Review)
Review
As the most potent professional antigen presenting cells, dendritic cells (DCs) have the ability to activate both naive CD4 and CD8 T cells. Recognized for their exceptional ability to cross-present exogenous antigens to prime naive antigen-specific CD8 T cells, DCs play a critical role in generating CD8 T cell immunity, as well as mediating CD8 T cell tolerance to tumor antigens. Despite the ability to potentiate host CD8 T cell-mediated anti-tumor immunity, current DC-based cancer vaccines have not yet achieved the promised success clinically with the exception of FDA-approved Provenge. Interestingly, recent studies have shown that type 1 conventional DCs (cDC1s) play a critical role in cross-priming tumor-specific CD8 T cells and determining the anti-tumor efficacy of cancer immunotherapies including immune checkpoint blockade (ICB). Together with promising clinical results in neoantigen-based cancer vaccines, there is a great need for DC-based vaccines to be further developed and refined either as monotherapies or in combination with other immunotherapies. In this review, we will present a brief review of DC development and function, discuss recent progress, and provide a perspective on future directions to realize the promising potential of DC-based cancer vaccines.
Topics: Humans; Antigen Presentation; Cancer Vaccines; Neoplasms; Antigens, Neoplasm; CD8-Positive T-Lymphocytes; Dendritic Cells
PubMed: 35946383
DOI: 10.1080/08820139.2022.2109486 -
Advances in Medical Sciences Sep 2022Antigen recognition and presentation are highlighted as the first steps in developing specialized antigen responses. Dendritic cells (DCs) are outstanding professional... (Review)
Review
Antigen recognition and presentation are highlighted as the first steps in developing specialized antigen responses. Dendritic cells (DCs) are outstanding professional antigen-presenting cells (APCs) responsible for priming cellular immunity in pathological states, including cancer. However, the diminished or repressed function of DCs is thought to be a substantial mechanism through which tumors escape from the immune system. In this regard, DCs obtained from breast cancer (BC) patients represent a notably weakened potency to encourage specific T-cell responses. Additionally, impaired DC-T-cell cross-talk in BC facilitates the immune evade of cancer cells and is connected with tumor advancement, immune tolerance, and adverse prognosis for patients. In this review we aim to highlight the available knowledge on DC-T-cell interactions in BC aggressiveness and show its therapeutic potential in BC treatment.
Topics: Humans; Female; T-Lymphocytes; Breast Neoplasms; Dendritic Cells
PubMed: 36116207
DOI: 10.1016/j.advms.2022.09.001 -
Frontiers in Immunology 2020Dendritic cells (DCs) are specialized antigen-presenting cells that play a key role in immune homeostasis and the adaptive immune response. DC-induced immune tolerance... (Review)
Review
Dendritic cells (DCs) are specialized antigen-presenting cells that play a key role in immune homeostasis and the adaptive immune response. DC-induced immune tolerance or activation is strictly dependent on the distinct maturation stages and migration ability of DCs. Ubiquitination is a reversible protein post-translational modification process that has emerged as a crucial mechanism that regulates DC maturation and function. Recent studies have shown that ubiquitin enzymes, including E3 ubiquitin ligases and deubiquitinases (DUBs), are pivotal regulators of DC-mediated immune function and serve as potential targets for DC-based immunotherapy of immune-related disorders (e.g., autoimmune disease, infections, and tumors). In this review, we summarize the recent progress regarding the molecular mechanisms and function of ubiquitination in DC-mediated immune homeostasis and immune response.
Topics: Animals; Cell Differentiation; Dendritic Cells; Humans; Protein Processing, Post-Translational; Ubiquitination
PubMed: 33329564
DOI: 10.3389/fimmu.2020.586613 -
Frontiers in Immunology 2023
Topics: Dendritic Cells; Biology
PubMed: 37234177
DOI: 10.3389/fimmu.2023.1206040 -
Methods in Molecular Biology (Clifton,... 2023Imaging of the immunological synapse (IS) between dendritic cells (DCs) and T cells in suspension is hampered by suboptimal alignment of cell-cell contacts along the...
Imaging of the immunological synapse (IS) between dendritic cells (DCs) and T cells in suspension is hampered by suboptimal alignment of cell-cell contacts along the vertical imaging plane. This requires optical sectioning that often results in unsatisfactory resolution in time and space. Here, we present a workflow where DCs and T cells are confined between a layer of glass and polydimethylsiloxane (PDMS) that orients the cells along one, horizontal imaging plane, allowing for fast en-face-imaging of the DC-T cell IS.
Topics: T-Lymphocytes; Immunological Synapses; Dendritic Cells; Lymphocyte Activation
PubMed: 37106180
DOI: 10.1007/978-1-0716-3135-5_9 -
Biomaterials Science Sep 2020Dendritic cells (DCs) are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. Understanding how...
Dendritic cells (DCs) are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. Understanding how biophysical properties affect DC behaviors will provide insight into the biology of a DC and its applications. In this work, we studied how cell culture dimensionality (two-dimensional (2D) and three-dimensional (3D)), and matrix density of 3D collagen matrices modulate differentiation and functions of DCs. Besides, we aimed to point out the different conceptual perspectives in modern immunological research, namely tissue-centric and cell-centric perspectives. The tissue-centric perspective intends to reveal how specific microenvironments dictate DC differentiation and in turn modulate DC functionalities, while the cell-centric perspective aims to demonstrate how pre-differentiated DCs behave in specific microenvironments. DC plasticity was characterized in terms of cell surface markers and cytokine secretion profiles. Subsequently, antigen internalization and T cell activation were quantified to demonstrate the cellular functions of immature DCs (iDCs) and mature DCs (mDCs), respectively. In the tissue-centric perspective, we found that expressed surface markers and secreted cytokines of both iDCs and mDCs are generally higher in 2D culture, while they are regulated by matrix density in 3D culture. In contrast, in the cell-centric perspective, we found enhanced expression of cell surface markers as well as distinct cytokine secretion profiles in both iDCs and mDCs. By analyzing cellular functions of cells in the tissue-centric perspective, we found matrix density dependence in antigen uptake by iDCs, as well as on mDC-mediated T cell proliferation in 3D cell culture. On the other hand, in the cell-centric perspective, both iDCs and mDCs appeared to lose their functional potentials to internalization antigen and T cell stimulation. Additionally, mDCs from tissue- and cell-centric perspectives modulated T cell differentiation by their distinct cytokine secretion profiles towards Th1 and Th17, respectively. In sum, our work emphasizes the importance of dimensionality, as well as collagen fibrillar density in the regulation of the immune response of DCs. Besides this, we demonstrated that the conceptual perspective of the experimental design could be an essential key point in research in immune cell-material interactions and biomaterial-based disease models of immunity.
Topics: Cell Differentiation; Cells, Cultured; Collagen; Cytokines; Dendritic Cells; Lymphocyte Activation
PubMed: 32812979
DOI: 10.1039/d0bm01141j