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Frontiers in Immunology 2018Professional antigen-presenting cells (APCs) include dendritic cells, monocytes, and B cells. APCs internalize and process antigens, producing immunogenic peptides that... (Review)
Review
Professional antigen-presenting cells (APCs) include dendritic cells, monocytes, and B cells. APCs internalize and process antigens, producing immunogenic peptides that enable antigen presentation to T lymphocytes, which provide the signals that trigger T-cell activation, proliferation, and differentiation, and lead to adaptive immune responses. After detection of microbial antigens through pattern recognition receptors (PRRs), APCs migrate to secondary lymphoid organs where antigen presentation to T lymphocytes takes place. Tetraspanins are membrane proteins that organize specialized membrane platforms, called tetraspanin-enriched microdomains, which integrate membrane receptors, like PRR and major histocompatibility complex class II (MHC-II), adhesion proteins, and signaling molecules. Importantly, through the modulation of the function of their associated membrane partners, tetraspanins regulate different steps of the immune response. Several tetraspanins can positively or negatively regulate the activation threshold of immune receptors. They also play a role during migration of APCs by controlling the surface levels and spatial arrangement of adhesion molecules and their subsequent intracellular signaling. Finally, tetraspanins participate in antigen processing and are important for priming of naïve T cells through the control of T-cell co-stimulation and MHC-II-dependent antigen presentation. In this review, we discuss the role of tetraspanins in APC biology and their involvement in effective immune responses.
Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Cell Movement; Dendritic Cells; Histocompatibility Antigens Class II; Humans; Immunomodulation; Protein Transport; Receptors, Pattern Recognition; Tetraspanins
PubMed: 29875769
DOI: 10.3389/fimmu.2018.01074 -
Frontiers in Immunology 2023
Topics: Dendritic Cells; Biology
PubMed: 37234177
DOI: 10.3389/fimmu.2023.1206040 -
Cancer Immunology, Immunotherapy : CII Oct 2007The discovery of tumor-associated antigens, which are either selectively or preferentially expressed by tumors, together with an improved insight in dendritic cell... (Review)
Review
The discovery of tumor-associated antigens, which are either selectively or preferentially expressed by tumors, together with an improved insight in dendritic cell biology illustrating their key function in the immune system, have provided a rationale to initiate dendritic cell-based cancer immunotherapy trials. Nevertheless, dendritic cell vaccination is in an early stage, as methods for preparing tumor antigen presenting dendritic cells and improving their immunostimulatory function are continuously being optimized. In addition, recent improvements in immunomonitoring have emphasized the need for careful design of this part of the trials. Still, valuable proofs-of-principle have been obtained, which favor the use of dendritic cells in subsequent, more standardized clinical trials. Here, we review the recent developments in clinical DC generation, antigen loading methods and immunomonitoring approaches for DC-based trials.
Topics: Antigen Presentation; Antigens, Neoplasm; Cancer Vaccines; Clinical Trials as Topic; Dendritic Cells; Humans; Immunotherapy; Monitoring, Immunologic; Neoplasms; Treatment Outcome
PubMed: 17503040
DOI: 10.1007/s00262-007-0334-z -
Journal of Immunology Research 2015Dendritic cells (DC) are professional antigen presenting cells and link the innate and adaptive immune system. During steady state immune surveillance in skin, DC act as... (Review)
Review
Dendritic cells (DC) are professional antigen presenting cells and link the innate and adaptive immune system. During steady state immune surveillance in skin, DC act as sentinels against commensals and invading pathogens. Under pathological skin conditions, inflammatory cytokines, secreted by surrounding keratinocytes, dermal fibroblasts, and immune cells, influence the activation and maturation of different DC populations including Langerhans cells (LC) and dermal DC. In this review we address critical differences in human DC subtypes during inflammatory settings compared to steady state. We also highlight the functional characteristics of human DC subsets in inflammatory skin environments and skin diseases including psoriasis and atopic dermatitis. Understanding the complex immunoregulatory role of distinct DC subsets in inflamed human skin will be a key element in developing novel strategies in anti-inflammatory therapy.
Topics: Animals; Cytokines; Dendritic Cells; Dermatitis; Humans; Immunomodulation; Inflammation; Inflammation Mediators
PubMed: 26229971
DOI: 10.1155/2015/743169 -
Immunobiology Feb 2015Based on their ability to balance tolerance and inflammation, antigen presenting cells, such as dendritic cells and macrophages contribute to the maintenance of immune... (Review)
Review
Based on their ability to balance tolerance and inflammation, antigen presenting cells, such as dendritic cells and macrophages contribute to the maintenance of immune homeostasis as well as the instigation of immune activation. Acting as key sensors of tissue integrity and pathogen invasion, they are well equipped with a wide variety of pattern recognition receptors, to which the C-type lectin family also belongs. C-type lectins are glycan-binding receptors that mediate cell-cell communication and pathogen recognition, besides participating in the endocytosis of antigens for presentation to T cells and the fine-tuning of immune responses. Here we review the current state-of-the-art on the dendritic cell and macrophage-expressed C-type lectin macrophage galactose-type lectin (MGL), highlighting the binding specificities, signaling properties and modulation of innate and adaptive immunity by its human and murine orthologues.
Topics: Adaptive Immunity; Animals; Carbohydrates; Dendritic Cells; Humans; Immunity, Innate; Immunomodulation; Lectins, C-Type; Ligands; Macrophages; Signal Transduction; Vaccination
PubMed: 25454488
DOI: 10.1016/j.imbio.2014.10.002 -
Mediators of Inflammation 2016Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the... (Review)
Review
Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential.
Topics: Animals; Dendritic Cells; Fatty Acids; Glycolysis; Humans; Immune Tolerance; Oxidative Phosphorylation
PubMed: 26980944
DOI: 10.1155/2016/2636701 -
Biochemical and Biophysical Research... Jul 2020The nuclear receptors REV-ERBα and REV-ERBβ have been demonstrated to play key roles in the regulation of numerous physiological functions, such as metabolism and the...
The nuclear receptors REV-ERBα and REV-ERBβ have been demonstrated to play key roles in the regulation of numerous physiological functions, such as metabolism and the circadian rhythm. Recent studies have established the REV-ERBs' roles in immunity, including macrophage and T cell responses. In contrast, their roles in dendritic cells have not been well defined. Dendritic cells are potent antigen presenting cells, connecting microbial sensing and innate immunity to adaptive immune responses. We demonstrate that both REV-ERBα and REV-ERBβ expression is upregulated during the course of bone marrow derived dendritic cell (BMDC) differentiation. BMDCs from REV-ERBα and REV-ERBβ deficient mice showed enhanced expression of maturation markers like CD86, MHCII, and proinflammatory cytokines. Conversely, treatment of BMDCs with a REV-ERB-specific agonist, SR9009, inhibited the expression of maturation markers and proinflammatory cytokines. Our study suggests the REV-ERBs act as negative regulators of dendritic cell development and activation. These results indicate that pharmacological modulation of REV-ERB activity could be an attractive strategy to modulate DC activation status and for DC-based therapies.
Topics: Animals; Bone Marrow Cells; Dendritic Cells; Female; Gene Deletion; Gene Expression Regulation, Developmental; Male; Mice, Inbred C57BL; Nuclear Receptor Subfamily 1, Group D, Member 1; Pyrrolidines; Receptors, Cytoplasmic and Nuclear; Repressor Proteins; Thiophenes
PubMed: 32439175
DOI: 10.1016/j.bbrc.2020.05.012 -
BioMed Research International 2015Glioblastoma multiforme (GBM) is the most malignant glioma and patients diagnosed with this disease had poor outcomes even treated with the combination of conventional... (Review)
Review
Glioblastoma multiforme (GBM) is the most malignant glioma and patients diagnosed with this disease had poor outcomes even treated with the combination of conventional treatment (surgery, chemotherapy, and radiation). Dendritic cells (DCs) are the most powerful antigen presenting cells and DC-based vaccination has the potential to target and eliminate GBM cells and enhance the responses of these cells to the existing therapies with minimal damage to the healthy tissues around them. It can enhance recognition of GBM cells by the patients' immune system and activate vast, potent, and long-lasting immune reactions to eliminate them. Therefore, this therapy can prolong the survival of GBM patients and has wide and bright future in the treatment of GBM. Also, the efficacy of this therapy can be strengthened in several ways at some degree: the manipulation of immune regulatory components or costimulatory molecules on DCs; the appropriate choices of antigens for loading to enhance the effectiveness of the therapy; regulation of positive regulators or negative regulators in GBM microenvironment.
Topics: Animals; Brain Neoplasms; Dendritic Cells; Glioblastoma; Humans; Immunotherapy; Mice; Models, Immunological
PubMed: 26167495
DOI: 10.1155/2015/717530 -
Clinical Medicine & Research Aug 2005The paradigm of tolerogenic/immature versus inflammatory/mature dendritic cells has dominated the recent literature regarding the role of these antigen-presenting cells... (Review)
Review
The paradigm of tolerogenic/immature versus inflammatory/mature dendritic cells has dominated the recent literature regarding the role of these antigen-presenting cells in mediating immune homeostasis or self-tolerance and response to pathogens, respectively. This issue is further complicated by the identification of distinct subtypes of dendritic cells that exhibit different antigen-presenting cell effector functions. The discovery of pathogen-associated molecular patterns and toll-like receptors provides the mechanistic basis for dendritic cell recognition of specific pathogens and induction of appropriate innate and adaptive immune responses. Only recently has insight been gained into how dendritic cells contribute to establishing and/or maintaining immunological tolerance to self. Soluble and cellular mediators have been reported to effectively regulate the function of dendritic cells by inducing several outcomes ranging from non-inflammatory dendritic cells that lack the ability to induce T lymphocyte activation to dendritic cells that actively suppress T lymphocyte responses. A thorough discussion of these stimuli and their outcomes is essential to understanding the potential for modulating dendritic cell function in the treatment of inflammatory disease conditions.
Topics: Animals; Apoptosis; Dendritic Cells; Humans; Immunity, Cellular; Immunologic Factors; T-Lymphocytes
PubMed: 16160071
DOI: 10.3121/cmr.3.3.166 -
Trends in Immunology Dec 2020Dendritic cells (DCs) have been classified into distinct subsets based on phenotype and ontogeny. In the past few years, high throughput single-cell approaches have... (Review)
Review
Dendritic cells (DCs) have been classified into distinct subsets based on phenotype and ontogeny. In the past few years, high throughput single-cell approaches have revealed further heterogeneity of human DCs, in particular at the transcriptomic level. Herein examined, are recent studies describing new human DC populations based on single-cell RNA-seq analysis, and a unified view of these emerging DC populations is presented. Also assessed are the features that define bona fide DC lineages, as opposed to cell states of the same lineage. Finally, where these newly described DC populations fit in the ontogeny-based classification of human DCs is examined.
Topics: Dendritic Cells; Humans; Phenotype; Transcriptome
PubMed: 33250080
DOI: 10.1016/j.it.2020.10.002