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Frontiers in Immunology 2020Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a linear acidic polysaccharide comprised of repeating disaccharides, modified with sulfate groups at... (Review)
Review
Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a linear acidic polysaccharide comprised of repeating disaccharides, modified with sulfate groups at various positions. Except for hyaluronan (HA), GAGs are covalently bound to core proteins, forming proteoglycans (PGs). With highly negative charges, GAGs interact with a variety of physiologically active molecules, including cytokines, chemokines, and growth factors, and control cell behavior during development and in the progression of diseases, including cancer, infections, and inflammation. Heparan sulfate (HS), another type of GAG, and HA are well reported as regulators for leukocyte migration at sites of inflammation. There have been many reports on the regulation of immune cell function by HS and HA; however, regulation of immune cells by CS has not yet been fully understood. This article focuses on the regulatory function of CS in antigen-presenting cells, including macrophages and dendritic cells, and refers to CSPGs, such as versican and biglycan, and the cell surface proteoglycan, syndecan.
Topics: Adaptive Immunity; Antigen-Presenting Cells; Biglycan; Carbohydrate Conformation; Carbohydrate Sequence; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Dendritic Cells; Humans; Hyaluronan Receptors; Immunity, Innate; Macrophages; Receptor-Like Protein Tyrosine Phosphatases, Class 2; Structure-Activity Relationship; Syndecans; Toll-Like Receptors; Versicans
PubMed: 32194548
DOI: 10.3389/fimmu.2020.00232 -
Cellular & Molecular Immunology Nov 2018Autophagy and immunity share the property of being auto-protective for the organism. Autophagy is an important degradation pathway that buffers nutrient deprivation by... (Review)
Review
Autophagy and immunity share the property of being auto-protective for the organism. Autophagy is an important degradation pathway that buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man. Perturbations in autophagy are associated with inflammation and cancer development. Emerging studies have characterized the molecular details regarding how autophagy is controlled by immune cells. Among these, dendritic cells (DCs) are one of the most potent professional antigen-presenting cells critical for the activation of naïve T cells to maintain immune tolerance and drive protective immunity to infection and cancer. DCs undergo functional maturation that can either lead to an immunostimulatory phenotype, as in the context of infection, or to a tolerogenic phenotype associated with immunosuppression to self-antigens, as well as to cancer. An increasing number of recent studies has characterized the involvement of autophagy in DC functions in various physiological and pathological contexts. Here, we provide a comprehensive review of these outcomes and discuss the limitation of the models used and the forefront of the knowledge concerning the crosstalk between autophagy and DC biology.
Topics: Animals; Autophagy; Dendritic Cells; Humans; Immune Tolerance; Immunity, Cellular; T-Lymphocytes
PubMed: 29578531
DOI: 10.1038/cmi.2018.2 -
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 -
Advanced Science (Weinheim,... Nov 2023Spleen and lymphoid organs are important targets for messenger RNA (mRNA) delivery in various applications. Current nanoparticle delivery methods rely on drainage to...
Spleen and lymphoid organs are important targets for messenger RNA (mRNA) delivery in various applications. Current nanoparticle delivery methods rely on drainage to lymph nodes from intramuscular or subcutaneous injections. In difficult-to-transfect antigen-presenting cells (APCs), such as dendritic cells (DCs), effective mRNA transfection remains a significant challenge. In this study, a lymphatic targeting carrier using DC membranes is developed, that efficiently migrated to lymphoid organs, such as the spleen and lymph nodes. The nanoparticles contained an ionizable lipid (YK009), which ensured a high encapsulation efficacy of mRNA and assisted mRNA with endosomal escape after cellular uptake. Dendritic cell-mimicking nanoparticles (DCMNPs) showed efficient protein expression in both the spleen and lymph nodes after intramuscular injections. Moreover, in immunized mice, DCMNP vaccination elicited Spike-specific IgG antibodies, neutralizing antibodies, and Th1-biased SARS-CoV-2-specific cellular immunity. This work presents a powerful vaccine formula using DCMNPs, which represents a promising vaccine candidate for further research and development.
Topics: Mice; Animals; Dendritic Cells; RNA, Messenger; Nanoparticles; Immunity, Cellular; Vaccines
PubMed: 37867227
DOI: 10.1002/advs.202302423 -
Molecular Carcinogenesis Feb 2022Presentation of tumor antigens is a critical step in producing a robust antitumor immune response. Classically tumor antigens are thought to be presented to both CD8 and... (Review)
Review
Presentation of tumor antigens is a critical step in producing a robust antitumor immune response. Classically tumor antigens are thought to be presented to both CD8 and CD4 T cells by professional antigen-presenting cells (pAPCs) like dendritic cells using major histocompatibility complexes (MHC) I and II. But recent evidence suggests that in the tumor microenvironment (TME) cells other than pAPCs are capable of presenting tumor antigens on both MHC I and II. The evidence currently available on tumor antigen presentation by epithelial cells, vascular endothelial cells (VECs), fibroblasts, and cancer cells is reviewed herein. We refer to these cell types in the TME as "amateur" APCs (aAPCs). These aAPCs greatly outnumber pAPCs in the TME and could, potentially, play a significant role in priming an antitumor immune response. This new evidence supports a different perspective on antigen presentation and suggests new approaches that can be taken in designing immunotherapies to increase T cell priming.
Topics: Antigen Presentation; Antigen-Presenting Cells; Antigens, Neoplasm; Dendritic Cells; Endothelial Cells; Humans; Tumor Microenvironment
PubMed: 34570920
DOI: 10.1002/mc.23354 -
Stem Cells (Dayton, Ohio) Nov 1995The recent discovery of multilineage donor leukocyte microchimerism in allograft recipients up to three decades after organ transplantation implies the migration and... (Review)
Review
The recent discovery of multilineage donor leukocyte microchimerism in allograft recipients up to three decades after organ transplantation implies the migration and survival of donor stem cells within the host. It has been postulated that in chimeric graft recipients, reciprocal modulation of immune responsiveness between donor and recipient leukocytes may lead, eventually, to the induction of mutual immunologic nonreactivity (tolerance). A prominent donor leukocyte, both in human organ transplant recipients and in animals, has invariably been the bone marrow-derived dendritic cell (DC). These cells have been classically perceived as the most potent antigen-presenting cells but evidence also exists for their tolerogenicity. The liver, despite its comparatively heavy leukocyte content, is the whole organ that is most capable of inducing tolerance. We have observed that DC progenitors propagated from normal mouse liver in response to GM-CSF express only low levels of major histocompatibility complex (MHC) class II antigen and little or no cell surface B7 family T cell costimulatory molecules. They fail to activate resting naive allogeneic T cells. When injected into normal allogeneic recipients, these DC progenitors migrate to T-dependent areas of host lymphoid tissue, where some at least upregulate cell surface MHC class II. These donor-derived cells persist indefinitely, recapitulating the behavior pattern of donor leukocytes after the successful transplantation of all whole organs, but most dramatically after the orthotopic (replacement) engraftment of the liver. A key finding is that in mice, progeny of these donor-derived DC progenitors can be propagated ex vivo from the bone marrow and other lymphoid tissues of nonimmunosuppressed spontaneously tolerant liver allograft recipients. In humans, donor DC can also be grown from the blood of organ allograft recipients whose organ-source chimerism is augmented with donor bone marrow infusion. DC progenitors cannot, however, be propagated from the lymphoid tissue of nonimmunosuppressed cardiac-allografted mice that reject their grafts. These findings are congruent with the possibility that bidirectional leukocyte migration and donor cell chimerism play key roles in acquired transplantation tolerance. Although the cell interactions are undoubtedly complex, a discrete role can be identified for DC under well-defined experimental conditions. Bone marrow-derived DC progenitors (MHC class II+, B7-1dim, B7-2-) induce alloantigen-specific hyporesponsiveness (anergy) in naive T cells in vitro. Moreover, costimulatory molecule-deficient DC progenitors administered systemically prolong the survival of mouse heart or pancreatic islet allografts. How the regulation of donor DC phenotype and function relates to the balance between the immunogenicity and tolerogenicity of organ allografts remains to be determined.
Topics: Animals; Dendritic Cells; Heart Transplantation; Host vs Graft Reaction; Humans; Immune Tolerance; Liver Transplantation; Mice; Stem Cells; Transplantation Chimera; Transplantation, Homologous
PubMed: 8590864
DOI: 10.1002/stem.5530130607 -
Frontiers in Immunology 2023With the deepening of our understanding of adaptive immunity at the cellular and molecular level, targeting antigens directly to immune cells has proven to be a... (Review)
Review
With the deepening of our understanding of adaptive immunity at the cellular and molecular level, targeting antigens directly to immune cells has proven to be a successful strategy to develop innovative and potent vaccines. Indeed, it offers the potential to increase vaccine potency and/or modulate immune response quality while reducing off-target effects. With mRNA-vaccines establishing themselves as a versatile technology for future applications, in the last years several approaches have been explored to target nanoparticles-enabled mRNA-delivery systems to immune cells, with a focus on dendritic cells. Dendritic cells (DCs) are the most potent antigen presenting cells and key mediators of B- and T-cell immunity, and therefore considered as an ideal target for cell-specific antigen delivery. Indeed, improved potency of DC-targeted vaccines has been proved and . This review discusses the potential specific targets for immune system-directed mRNA delivery, as well as the different targeting ligand classes and delivery systems used for this purpose.
Topics: Dendritic Cells; Vaccines; Adaptive Immunity; T-Lymphocytes; Antigens
PubMed: 38090568
DOI: 10.3389/fimmu.2023.1294929 -
Human Vaccines & Immunotherapeutics Mar 2016Dendritic cells (DCs) are known to be a set of morphology, structure and function of heterogeneous professional antigen presenting cells (APCs), as well as the strongest...
Dendritic cells (DCs) are known to be a set of morphology, structure and function of heterogeneous professional antigen presenting cells (APCs), as well as the strongest functional antigen presenting cells, which can absorb, process and present antigens. As the key regulators of innate and adaptive immune responses, DCs are at the center of the immune system and capable of interacting with both B cells and T cells, thereby manipulating the humoral and cellular immune responses. DCs provide an essential link between the innate and adaptive immunity, and the strong immune activation function of DCs and their properties of natural adjuvants, make them a valuable target for antigen delivery. Targeting antigens to DC-specific endocytic receptors in combination with the relevant antibodies or ligands along with immunostimulatory adjuvants has been recently recognized as a promising strategy for designing an effective vaccine that elicits a strong and durable T cell response against intracellular pathogens and cancer. This opinion article provides a brief summary of the rationales, superiorities and challenges of existing DC-targeting approaches.
Topics: Adaptive Immunity; Animals; Antigen Presentation; Dendritic Cells; Humans; Immunity, Innate; T-Lymphocytes; Vaccines
PubMed: 26513200
DOI: 10.1080/21645515.2015.1105415 -
Immunology Aug 2011Dendritic cells (DCs) are professional antigen-presenting cells that are critical for induction of adaptive immunity and tolerance. Traditionally DCs have been divided... (Review)
Review
Dendritic cells (DCs) are professional antigen-presenting cells that are critical for induction of adaptive immunity and tolerance. Traditionally DCs have been divided into two discrete subtypes, which comprise conventional and non-conventional DCs. They are distributed across various organs in the body and comprise a heterogeneous population, which has been shown to display differences in terms of surface marker expression, function and origins. Recent studies have shed new light on the process of DC differentiation and distribution of DC subtypes in various organs. Although monocytes, macrophages and DCs share a common macrophage-DC progenitor, a common DC progenitor population has been identified that exclusively gives rise to DCs and not monocytes or macrophages. In this review, we discuss the recent advances in our understanding of DC differentiation and subtypes and provide a comprehensive overview of various DC subtypes with emphasis on their function and origins. Furthermore, in light of recent developments in the field of DC biology, we classify DCs based on the precursor populations from which the various DC subsets originate. We classify DCs derived from common DC progenitor and pre-DC populations as conventional DCs, which includes both migratory and lymphoid-resident DC subsets and classify monocyte-derived DCs and plasmacytoid DCs as non-conventional DCs.
Topics: Animals; Cell Differentiation; Dendritic Cells; Humans; Immune System
PubMed: 21627652
DOI: 10.1111/j.1365-2567.2011.03457.x -
Microbes and Infection Jun 2010Immunological synapses (IS) are emerging as highly organized 3D structures -formed by surface and cytoplasmic signalling and cytoskeletal molecules - that assemble at... (Review)
Review
Immunological synapses (IS) are emerging as highly organized 3D structures -formed by surface and cytoplasmic signalling and cytoskeletal molecules - that assemble at the zone of contact between a T cell and an antigen presenting cell (APC). The IS control functions that allow APC and T cells modulate the immune response.
Topics: Animals; Antigen-Presenting Cells; Cell Communication; Cytoskeletal Proteins; Dendritic Cells; Humans; Immunological Synapses; Signal Transduction; T-Lymphocytes
PubMed: 20227515
DOI: 10.1016/j.micinf.2010.03.003