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International Review of Cell and... 2019Dendritic cells (DCs) are a unique class of immune cells that act as a bridge between innate and adaptive immunity. The discovery of DCs by Cohen and Steinman in 1973... (Review)
Review
Dendritic cells (DCs) are a unique class of immune cells that act as a bridge between innate and adaptive immunity. The discovery of DCs by Cohen and Steinman in 1973 laid the foundation for DC biology, and the advances in the field identified different versions of DCs with unique properties and functions. DCs originate from hematopoietic stem cells, and their differentiation is modulated by Flt3L. They are professional antigen-presenting cells that patrol the environmental interphase, sites of infection, or infiltrate pathological tissues looking for antigens that can be used to activate effector cells. DCs are critical for the initiation of the cellular and humoral immune response and protection from infectious diseases or tumors. DCs can take up antigens using specialized surface receptors such as endocytosis receptors, phagocytosis receptors, and C type lectin receptors. Moreover, DCs are equipped with an array of extracellular and intracellular pattern recognition receptors for sensing different danger signals. Upon sensing the danger signals, DCs get activated, upregulate costimulatory molecules, produce various cytokines and chemokines, take up antigen and process it and migrate to lymph nodes where they present antigens to both CD8 and CD4 T cells. DCs are classified into different subsets based on an integrated approach considering their surface phenotype, expression of unique and conserved molecules, ontogeny, and functions. They can be broadly classified as conventional DCs consisting of two subsets (DC1 and DC2), plasmacytoid DCs, inflammatory DCs, and Langerhans cells.
Topics: Animals; Dendritic Cells; Humans
PubMed: 31810551
DOI: 10.1016/bs.ircmb.2019.07.004 -
Immunity Aug 2023Conventional dendritic cells (cDCs) are professional antigen-presenting cells that control the adaptive immune response. Their subsets and developmental origins have...
Conventional dendritic cells (cDCs) are professional antigen-presenting cells that control the adaptive immune response. Their subsets and developmental origins have been intensively investigated but are still not fully understood as their phenotypes, especially in the DC2 lineage and the recently described human DC3s, overlap with monocytes. Here, using LEGENDScreen to profile DC vs. monocyte lineages, we found sustained expression of FLT3 and CD45RB through the whole DC lineage, allowing DCs and their precursors to be distinguished from monocytes. Using fate mapping models, single-cell RNA sequencing and adoptive transfer, we identified a lineage of murine CD16/32CD172a DC3, distinct from DC2, arising from Ly6C monocyte-DC progenitors (MDPs) through Lyz2Ly6CCD11c pro-DC3s, whereas DC2s develop from common DC progenitors (CDPs) through CD7Ly6CCD11c pre-DC2s. Corresponding DC subsets, developmental stages, and lineages exist in humans. These findings reveal DC3 as a DC lineage phenotypically related to but developmentally different from monocytes and DC2s.
Topics: Mice; Humans; Animals; Monocytes; Stem Cells; Phenotype; Cells, Cultured; Dendritic Cells; Cell Differentiation
PubMed: 37506694
DOI: 10.1016/j.immuni.2023.07.001 -
Immunology May 2018Dendritic cells (DC) are a class of bone-marrow-derived cells arising from lympho-myeloid haematopoiesis that form an essential interface between the innate sensing of... (Review)
Review
Dendritic cells (DC) are a class of bone-marrow-derived cells arising from lympho-myeloid haematopoiesis that form an essential interface between the innate sensing of pathogens and the activation of adaptive immunity. This task requires a wide range of mechanisms and responses, which are divided between three major DC subsets: plasmacytoid DC (pDC), myeloid/conventional DC1 (cDC1) and myeloid/conventional DC2 (cDC2). Each DC subset develops under the control of a specific repertoire of transcription factors involving differential levels of IRF8 and IRF4 in collaboration with PU.1, ID2, E2-2, ZEB2, KLF4, IKZF1 and BATF3. DC haematopoiesis is conserved between mammalian species and is distinct from monocyte development. Although monocytes can differentiate into DC, especially during inflammation, most quiescent tissues contain significant resident populations of DC lineage cells. An extended range of surface markers facilitates the identification of specific DC subsets although it remains difficult to dissociate cDC2 from monocyte-derived DC in some settings. Recent studies based on an increasing level of resolution of phenotype and gene expression have identified pre-DC in human blood and heterogeneity among cDC2. These advances facilitate the integration of mouse and human immunology, support efforts to unravel human DC function in vivo and continue to present new translational opportunities to medicine.
Topics: Biomarkers; Cell Communication; Cell Differentiation; Dendritic Cells; Humans; Immunity; Immunophenotyping; Kruppel-Like Factor 4; Phenotype; Signal Transduction
PubMed: 29313948
DOI: 10.1111/imm.12888 -
Annual Review of Immunology Apr 2021As the professional antigen-presenting cells of the immune system, dendritic cells (DCs) sense the microenvironment and shape the ensuing adaptive immune response. DCs... (Review)
Review
As the professional antigen-presenting cells of the immune system, dendritic cells (DCs) sense the microenvironment and shape the ensuing adaptive immune response. DCs can induce both immune activation and immune tolerance according to the peripheral cues. Recent work has established that DCs comprise several phenotypically and functionally heterogeneous subsets that differentially regulate T lymphocyte differentiation. This review summarizes both mouse and human DC subset phenotypes, development, diversification, and function. We focus on advances in our understanding of how different DC subsets regulate distinct CD4 T helper (Th) cell differentiation outcomes, including Th1, Th2, Th17, T follicular helper, and T regulatory cells. We review DC subset intrinsic properties, local tissue microenvironments, and other immune cells that together determine Th cell differentiation during homeostasis and inflammation.
Topics: Animals; Dendritic Cells; Humans; Immune Tolerance; Lymphocyte Activation; Mice; T-Lymphocytes, Regulatory; Th17 Cells
PubMed: 33710920
DOI: 10.1146/annurev-immunol-101819-025146 -
Cell Research Jan 2017Immunotherapy using dendritic cell (DC)-based vaccination is an approved approach for harnessing the potential of a patient's own immune system to eliminate tumor cells... (Review)
Review
Immunotherapy using dendritic cell (DC)-based vaccination is an approved approach for harnessing the potential of a patient's own immune system to eliminate tumor cells in metastatic hormone-refractory cancer. Overall, although many DC vaccines have been tested in the clinic and proven to be immunogenic, and in some cases associated with clinical outcome, there remains no consensus on how to manufacture DC vaccines. In this review we will discuss what has been learned thus far about human DC biology from clinical studies, and how current approaches to apply DC vaccines in the clinic could be improved to enhance anti-tumor immunity.
Topics: Animals; Antigen Presentation; Antigens, Neoplasm; Dendritic Cells; Humans; Immunity; Immunotherapy; Vaccination
PubMed: 28025976
DOI: 10.1038/cr.2016.157 -
Cellular & Molecular Immunology May 2023Dendritic cells (DCs) exhibit a specialized antigen-presenting function and play crucial roles in both innate and adaptive immune responses. Due to their ability to... (Review)
Review
Dendritic cells (DCs) exhibit a specialized antigen-presenting function and play crucial roles in both innate and adaptive immune responses. Due to their ability to cross-present tumor cell-associated antigens to naïve T cells, DCs are instrumental in the generation of specific T-cell-mediated antitumor effector responses in the control of tumor growth and tumor cell dissemination. Within an immunosuppressive tumor microenvironment, DC antitumor functions can, however, be severely impaired. In this review, we focus on the mechanisms of DC capture and activation by tumor cell antigens and the role of the tumor microenvironment in shaping DC functions, taking advantage of recent studies showing the phenotype acquisition, transcriptional state and functional programs revealed by scRNA-seq analysis. The therapeutic potential of DC-mediated tumor antigen sensing in priming antitumor immunity is also discussed.
Topics: Humans; Dendritic Cells; Neoplasms; Antigens, Neoplasm; T-Lymphocytes; Tumor Microenvironment
PubMed: 36949244
DOI: 10.1038/s41423-023-00990-6 -
Seminars in Cell & Developmental Biology Dec 2018Dendritic cells (DC) are professional antigen presenting cells comprising a variety of subsets, as either resident or migrating cells, in lymphoid and non-lymphoid... (Review)
Review
Dendritic cells (DC) are professional antigen presenting cells comprising a variety of subsets, as either resident or migrating cells, in lymphoid and non-lymphoid organs. In the steady state DC continually process and present antigens on MHCI and MHCII, processes that are highly upregulated upon activation. By expressing differential sets of pattern recognition receptors different DC subsets are able to respond to a range of pathogenic and danger stimuli, enabling functional specialisation of the DC. The knowledge of functional specialisation of DC subsets is key to efficient priming of T cells, to the design of effective vaccine adjuvants and to understanding the role of different DC in health and disease. This review outlines mouse and human steady state DC subsets and key attributes that define their distinct functions.
Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Cell Differentiation; Dendritic Cells; Humans; Lymphocyte Activation; T-Lymphocytes
PubMed: 29246859
DOI: 10.1016/j.semcdb.2017.12.009 -
Annual Review of Virology Sep 2019More than 80 different adenovirus (AdV) types infect humans through the respiratory, ocular, or gastrointestinal tracts. They cause acute clinical mani-festations or... (Review)
Review
More than 80 different adenovirus (AdV) types infect humans through the respiratory, ocular, or gastrointestinal tracts. They cause acute clinical mani-festations or persist under humoral and cell-based immunity. Immuno-suppressed individuals are at risk of death from an AdV infection. Concepts about cell entry of AdV build on strong foundations from molecular and cellular biology-and increasingly physical virology. Here, we discuss how virions enter and deliver their genome into the nucleus of epithelial cells. This process breaks open the virion at distinct sites because the particle has nonisometric mechanical strength and reacts to specific host factors along the entry pathway. We further describe how macrophages and dendritic cells resist AdV infection yet enhance productive entry into polarized epithelial cells. A deep understanding of the viral mechanisms and cell biological and biophysical principles will continue to unravel how epithelial and antigen-presenting cells respond to AdVs and control inflammation and persistence in pathology and therapy.
Topics: Adenoviridae; Adenoviridae Infections; Animals; Antigen-Presenting Cells; Dendritic Cells; Epithelial Cells; Humans; Macrophages; Mice; Virion; Virus Internalization; Virus Replication
PubMed: 31283442
DOI: 10.1146/annurev-virology-092818-015550 -
Nature Reviews. Immunology Jan 2017Dendritic cells (DCs) are potent and versatile antigen-presenting cells, and their ability to migrate is key for the initiation of protective pro-inflammatory as well as... (Review)
Review
Dendritic cells (DCs) are potent and versatile antigen-presenting cells, and their ability to migrate is key for the initiation of protective pro-inflammatory as well as tolerogenic immune responses. Recent comprehensive studies have highlighted the importance of DC migration in the maintenance of immune surveillance and tissue homeostasis, and also in the pathogenesis of a range of diseases. In this Review, we summarize the anatomical, cellular and molecular factors that regulate the migration of different DC subsets in health and disease. In particular, we focus on new insights concerning the role of migratory DCs in the pathogenesis of diseases of the skin, intestine, lung, and brain, as well as in autoimmunity and atherosclerosis.
Topics: Animals; Autoimmunity; Cell Movement; Dendritic Cells; Humans; Immune Tolerance
PubMed: 27890914
DOI: 10.1038/nri.2016.116 -
Frontiers in Immunology 2020Despite significant advances in the field of cancer immunotherapy, the majority of patients still do not benefit from treatment and must rely on traditional therapies.... (Review)
Review
Despite significant advances in the field of cancer immunotherapy, the majority of patients still do not benefit from treatment and must rely on traditional therapies. Dendritic cells have long been a focus of cancer immunotherapy due to their role in inducing protective adaptive immunity, but cancer vaccines have shown limited efficacy in the past. With the advent of immune checkpoint blockade and the ability to identify patient-specific neoantigens, new vaccines, and combinatorial therapies are being evaluated in the clinic. Dendritic cells are also emerging as critical regulators of the immune response within tumors. Understanding how to augment the function of these intratumoral dendritic cells could offer new approaches to enhance immunotherapy, in addition to improving the cytotoxic and targeted therapies that are partially dependent upon a robust immune response for their efficacy. Here we will discuss the role of specific dendritic cell subsets in regulating the anti-tumor immune response, as well as the current status of dendritic cell-based immunotherapies, in order to provide an overview for future lines of research and clinical trials.
Topics: Animals; Antineoplastic Agents, Immunological; Cancer Vaccines; Dendritic Cells; Humans; Immune Checkpoint Inhibitors; Immunotherapy, Adoptive; Neoplasms; Phenotype; Signal Transduction; Treatment Outcome
PubMed: 32508825
DOI: 10.3389/fimmu.2020.00924