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Seminars in Immunology Dec 2015Dendritic cells (DCs) are uniquely potent in orchestrating T cell immune response, thus they are indispensable immune sentinels. They originate from progenitors in the... (Review)
Review
Dendritic cells (DCs) are uniquely potent in orchestrating T cell immune response, thus they are indispensable immune sentinels. They originate from progenitors in the bone marrow through hematopoiesis, a highly regulated developmental process involving multiple cellular and molecular events. This review highlights studies of DC development-from the discovery of DCs as glass-adherent antigen presenting cells to the debate and resolution of their origin and lineage map. In particular, we summarize the roles of lineage-specific cytokines, the placement of distinct hematopoietic progenitors within the DC lineage and transcriptional programs governing DC development, which together have allowed us to diagram the current view of DC hematopoiesis. Important open questions and debates on the DC development and relevant models are also discussed.
Topics: Animals; Cell Differentiation; Cell Lineage; Dendritic Cells; Hematopoiesis; Humans
PubMed: 27040276
DOI: 10.1016/j.smim.2016.03.012 -
Seminars in Immunology Mar 2023Cross-priming was first recognized in the context of in vivo cytotoxic T lymphocyte (CTL) responses generated against minor histocompatibility antigens induced by... (Review)
Review
Cross-priming was first recognized in the context of in vivo cytotoxic T lymphocyte (CTL) responses generated against minor histocompatibility antigens induced by immunization with lymphoid cells. Even though the basis for T cell antigen recognition was still largely unclear at that time, these early studies recognized the implication that such minor histocompatibility antigens were derived from the immunizing cells and were obtained exogenously by the host's antigen presenting cells (APCs) that directly prime the CTL response. As antigen recognition by the T cell receptor became understood to involve peptides derived from antigens processed by the APCs and presented by major histocompatibility molecules, the "cross-priming" phenomenon was subsequently recast as "cross-presentation" and the scope considered for examining this process gradually broadened to include many different forms of antigens, including soluble proteins, and different types of APCs that may not be involved in in vivo CTL priming. Many studies of cross-presentation have relied on in vitro cell models that were recently found to differ from in vivo APCs in particular mechanistic details. A recent trend has focused on the APCs and pathways of cross-presentation used in vivo, especially the type 1 dendritic cells. Current efforts are also being directed towards validating the in vivo role of various putative pathways and gene candidates in cross-presentation garnered from various in vitro studies and to determine the relative contributions they make to CTL responses across various forms of antigens and immunologic settings. Thus, cross-presentation appears to be carried by different pathways in various types of cells for different forms under different physiologic settings, which remain to be evaluated in an in vivo physiologic setting.
Topics: Humans; Antigen-Presenting Cells; Cross-Priming; T-Lymphocytes, Cytotoxic; Antigens; Minor Histocompatibility Antigens; Biology; Dendritic Cells; Antigen Presentation; Histocompatibility Antigens Class I
PubMed: 36645993
DOI: 10.1016/j.smim.2023.101711 -
International Journal of Pharmaceutics May 2018Crosstalk among immune cells has attracted considerable attention with the advent of immunotherapy as a novel therapeutic approach for challenging diseases, especially... (Review)
Review
Crosstalk among immune cells has attracted considerable attention with the advent of immunotherapy as a novel therapeutic approach for challenging diseases, especially cancer, which is the leading cause of mortality worldwide. Dendritic cells-the key antigen-presenting cells-play a pivotal role in immunological response by presenting exogenous epitopes to T cells, which induces the self-defense mechanisms of the body. Furthermore, nanotechnology has provided promising ways for diagnosing and treating cancer in the last decade. The progress in nanoparticle drug carrier development, combined with enhanced understanding of the immune system, has enabled harnessing of anti-tumor immunity. This review focuses on the recent advances in nanotechnology that have improved the therapeutic efficacy of immunotherapies, with emphasis on dendritic cell physiology and its role in presenting antigens and eliciting therapeutic T cell response.
Topics: Animals; Dendritic Cells; Humans; Immunotherapy; Nanoparticles
PubMed: 29555438
DOI: 10.1016/j.ijpharm.2018.03.029 -
International Review of Cell and... 2019Dendritic cells (DCs) are major regulators of adaptive immunity, as they are not only capable to induce efficient immune responses, but are also crucial to maintain... (Review)
Review
Dendritic cells (DCs) are major regulators of adaptive immunity, as they are not only capable to induce efficient immune responses, but are also crucial to maintain peripheral tolerance and thereby inhibit autoimmune reactions. DCs bridge the innate and the adaptive immune system by presenting peptides of self and foreign antigens as peptide MHC complexes to T cells. These properties render DCs as interesting target cells for immunomodulatory therapies in cancer, but also autoimmune diseases. Several subsets of DCs with special properties and functions have been described. Recent achievements in understanding transcriptional programs on single cell level, together with the generation of new murine models targeting specific DC subsets, advanced our current understanding of DC development and function. Thus, DCs arise from precursor cells in the bone marrow with distinct progenitor cell populations splitting the monocyte populations and macrophage populations from the DC lineage, which upon lineage commitment can be separated into conventional cDC1, cDC2, and plasmacytoid DCs (pDCs). The DC populations harbor intrinsic programs enabling them to react for specific pathogens in dependency on the DC subset, and thereby orchestrate T cell immune responses. Similarities, but also varieties, between human and murine DC subpopulations are challenging, and will require further investigation of human specimens under consideration of the influence of the tissue micromilieu and DC subset localization in the future.
Topics: Animals; Dendritic Cells; Epigenesis, Genetic; Humans; Phenotype; Transcription Factors; Transcription, Genetic
PubMed: 31759434
DOI: 10.1016/bs.ircmb.2019.10.001 -
Current Opinion in Biotechnology Apr 2022Immune instructive materials, are materials with the ability to modulate or mimic the function of immune cells, provide exciting opportunities for developing new... (Review)
Review
Immune instructive materials, are materials with the ability to modulate or mimic the function of immune cells, provide exciting opportunities for developing new therapies in many areas including medical devices, chronic inflammation, cancer, and autoimmune diseases. In this review we highlight some of the latest research involving material-based strategies for modulating macrophage phenotype and dendritic cell function, as well as a brief description on biomaterial use in T cell and natural killer cell engineering. We highlight studies on material topography, size, shape and surface chemistry to reduce inflammation, along with scaffold and hydrogel delivery systems that are used for modulating DC phenotype and influencing T cell polarization. Artificial antigen presenting cells are also reviewed as a promising approach to cancer immunotherapy.
Topics: Biocompatible Materials; Dendritic Cells; Humans; Immunotherapy; Inflammation; Neoplasms
PubMed: 34959210
DOI: 10.1016/j.copbio.2021.11.005 -
Molecular Neurobiology Jan 2022Dendritic cells (DCs) are the immune system's highly specialized antigen-presenting cells. When DCs are sluggish and mature, self-antigen presentation results in... (Review)
Review
Dendritic cells (DCs) are the immune system's highly specialized antigen-presenting cells. When DCs are sluggish and mature, self-antigen presentation results in tolerance; however, when pathogen-associated molecular patterns stimulate mature DCs, antigen presentation results in the development of antigen-specific immunity. DCs have been identified in various vital organs of mammals (e.g., the skin, heart, lungs, intestines, and spleen), but the brain has long been thought to be devoid of DCs in the absence of neuroinflammation. However, neuroinflammation is becoming more recognized as a factor in a variety of brain illnesses. DCs are present in the brain parenchyma in trace amounts under healthy circumstances, but their numbers rise during neuroinflammation. New therapeutics are being developed that can reduce dendritic cell immunogenicity by inhibiting pro-inflammatory cytokine production and T cell co-stimulatory pathways. Additionally, innovative ways of regulating dendritic cell growth and differentiation and harnessing their tolerogenic capability are being explored. Herein, we described the function of dendritic cells in neurological disorders and discussed the potential for future therapeutic techniques that target dendritic cells and dendritic cell-related targets in the treatment of neurological disorders.
Topics: Animals; Dendritic Cells; Drug Delivery Systems; Humans; Immune Tolerance; Nervous System Diseases
PubMed: 34743292
DOI: 10.1007/s12035-021-02622-4 -
Methods in Molecular Biology (Clifton,... 2019Since the 1997 discovery that the first identified human homolog of Drosophila Toll could activate the innate immune system, the innate arm of immunity has rapidly taken...
Since the 1997 discovery that the first identified human homolog of Drosophila Toll could activate the innate immune system, the innate arm of immunity has rapidly taken on a new light as an important player in the recognition of pathogens and damaged self. The recognition of danger by dendritic cells (DC) is a crucial step in activating the adaptive immune system. Different DC express varied subsets of pattern recognition receptors (PRR), enabling both overlap and exclusivity in the recognition of danger signals by DC. PRR-mediated DC maturation and activation can be measured by changes in the surface expression of costimulatory as well as coinhibitory molecules, changes in size and shape of the DC and by their production of different cytokines.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cell Membrane; Cells, Cultured; Dendritic Cells; Humans; Mice, Inbred C57BL; Staining and Labeling
PubMed: 31147955
DOI: 10.1007/978-1-4939-9450-2_28 -
Methods in Molecular Biology (Clifton,... 2016Dendritic cells are specialized antigen-presenting cells that initiate and orient immune responses. Numerous studies in mice and humans have shown that dendritic cells... (Review)
Review
Dendritic cells are specialized antigen-presenting cells that initiate and orient immune responses. Numerous studies in mice and humans have shown that dendritic cells are heterogeneous and comprise several subsets that can be distinguished by their surface phenotype, ontogeny, and molecular signature. This review gives an overview of mouse and human dendritic cell subsets and their defining features and summarizes the current knowledge of dendritic cell subsets' functional specialization in terms of antigen presentation.
Topics: Animals; Antigen Presentation; Biomarkers; Cell Lineage; Dendritic Cells; Humans; Mice
PubMed: 27142005
DOI: 10.1007/978-1-4939-3606-9_1 -
Journal of Leukocyte Biology Mar 2022Dendritic cells (DCs) are efficient antigen-presenting cells that serve as a link between the innate and adaptive immune systems. These cells are broadly involved in... (Review)
Review
Dendritic cells (DCs) are efficient antigen-presenting cells that serve as a link between the innate and adaptive immune systems. These cells are broadly involved in cellular and humoral immune responses by presenting antigens to initiate T cell reactions, cytokine and chemokine secretion, T cell differentiation and expansion, B cell activation and regulation, and the mediation of immune tolerance. The functions of DCs depend on their activation status, which is defined by the stages of maturation, phenotype differentiation, and migration ability, among other factors. IL-6 is a soluble mediator mainly produced by a variety of immune cells, including DCs, that exerts pleiotropic effects on immune and inflammatory responses through interaction with specific receptors expressed on the surface of target cells. Here, we review the role of IL-6, when generated in an inflammatory context or as derived from DCs, in modulating the biologic function and activation status of DCs and emphasize the importance of searching for novel strategies to target the IL-6/IL-6 signaling pathway as a means to diminish the inflammatory activity of DCs in immune response or to prime the immunogenic activity of DCs in immunosuppressive conditions.
Topics: Cell Differentiation; Dendritic Cells; Immune Tolerance; Interleukin-6; Lymphocyte Activation; T-Lymphocytes
PubMed: 34405445
DOI: 10.1002/JLB.3MR0621-616RR -
Journal of Autoimmunity Dec 2017Dendritic cells (DCs) are professional antigen presenting cells displaying the unique capability to activate naïve T cells. DCs react to pathogen encounter also by the... (Review)
Review
Dendritic cells (DCs) are professional antigen presenting cells displaying the unique capability to activate naïve T cells. DCs react to pathogen encounter also by the production of mediators of inflammation, including pro-inflammatory cytokines. Because of this complex role, any imbalance in DC function reflects into defective or exaggerated immune response and tissue damage. DCs comprise two main subsets, namely conventional or classical DCs (cDCs), that are dedicated antigen presenting cells, and plasmacytoid DCs (pDCs), that respond to nucleic acids by releasing high amounts of type I interferons (IFNs). Since the formal demonstration that DC can prime autoreactive naïve T cells, a full body of evidence has implicated DCs in virtually all manifestations of autoimmunity, although their exact pathogenic role often remains poorly characterized. The recent availability of progressively more refined strategies of constitutive and inducible DC ablation is contributing in defining the precise role of DCs at least in some autoimmune disease models. This review aims at critically summarizing the current literature concerning selected aspects of DC biology that, when altered, facilitate autoimmunity. These aspects include: i) mechanisms of tissue entry and accumulation, ii) mechanisms of activation and iii) orchestration of the immune balance by cytokine production. A special focus will be on inappropriate DC activation by signals released by damaged tissues via innate immune receptors, such as Toll-like receptors. These signals are responsible, in pDCs, for exaggerated type I IFN production, the hallmark of a set of apparently distant autoimmune conditions such as systemic lupus erythematosus and type 1 diabetes; whereas in cDCs, they trigger DC rapid maturation and Th1/Th17 cytokine secretion. Tissue-derived molecules also contribute to further promote tissue damage and autoantigen spreading, possibly through pDC-derived Granzyme B secretion. Finally, the therapeutic possibilities based on DC targeting in human autoimmune diseases will be briefly summarized.
Topics: Animals; Autoimmune Diseases; Autoimmunity; Cytokines; Dendritic Cells; Humans; Immunity, Innate
PubMed: 28774715
DOI: 10.1016/j.jaut.2017.07.012