Review

Authors: Matthew Collin, Venetia Bigley

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

Review

Authors: Laura Tiberio, Annalisa Del Prete, Tiziana Schioppa...

Dendritic cells (DCs) are professional antigen-presenting cells responsible for the activation of specific T-cell responses and for the development of immune tolerance. Immature DCs reside in peripheral tissues and specialize in antigen capture, whereas mature DCs reside mostly in the secondary lymphoid organs where they act as antigen-presenting cells. The correct localization of DCs is strictly regulated by a large variety of chemotactic and nonchemotactic signals that include bacterial products, DAMPs (danger-associated molecular patterns), complement proteins, lipids, and chemokines. These signals function both individually and in concert, generating a complex regulatory network. This network is regulated at multiple levels through different strategies, such as synergistic interactions, proteolytic processing, and the actions of atypical chemokine receptors. Understanding this complex scenario will help to clarify the role of DCs in different pathological conditions, such as autoimmune diseases and cancers and will uncover new molecular targets for therapeutic interventions.

Topics: Animals; Cell Movement; Chemokines; Chemotaxis; Dendritic Cells; Humans; Receptors, Chemokine; Signal Transduction

PubMed: 29563613
DOI: 10.1038/s41423-018-0005-3

Authors: Domenico Galati, Serena Zanotta

Dendritic cells (DCs) are acknowledged as the most potent professional antigen-presenting cells (APCs), able to induce adaptive immunity and support the innate immune response [...].

Topics: Humans; Dendritic Cells; Adaptive Immunity; Immunity, Innate; Neoplasms

PubMed: 36835665
DOI: 10.3390/ijms24044253

Review

Authors: Thiago A Patente, Mariana P Pinho, Aline A Oliveira...

Dendritic cells (DC) are professional antigen presenting cells, uniquely able to induce naïve T cell activation and effector differentiation. They are, likewise, involved in the induction and maintenance of immune tolerance in homeostatic conditions. Their phenotypic and functional heterogeneity points to their great plasticity and ability to modulate, according to their microenvironment, the acquired immune response and, at the same time, makes their precise classification complex and frequently subject to reviews and improvement. This review will present general aspects of the DC physiology and classification and will address their potential and actual uses in the management of human disease, more specifically cancer, as therapeutic and monitoring tools. New combination treatments with the participation of DC will be also discussed.

Topics: Animals; Biomarkers; Cancer Vaccines; Cell Differentiation; Combined Modality Therapy; Dendritic Cells; Humans; Immune System; Immune System Phenomena; Immunotherapy; Neoplasms; Phenotype; Treatment Outcome; Tumor Microenvironment

PubMed: 30719026
DOI: 10.3389/fimmu.2018.03176

Review

Authors: Charlotte M de Winde, Clare Munday, Sophie E Acton...

Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells that act to bridge innate and adaptive immunity. DCs are critical in mounting effective immune responses to tissue damage, pathogens and cancer. Immature DCs continuously sample tissues and engulf antigens via endocytic pathways such as phagocytosis or macropinocytosis, which result in DC activation. Activated DCs undergo a maturation process by downregulating endocytosis and upregulating surface proteins controlling migration to lymphoid tissues where DC-mediated antigen presentation initiates adaptive immune responses. To traffic to lymphoid tissues, DCs must adapt their motility mechanisms to migrate within a wide variety of tissue types and cross barriers to enter lymphatics. All steps of DC migration involve cell-cell or cell-substrate interactions. This review discusses DC migration mechanisms in immunity and cancer with a focus on the role of cytoskeletal processes and cell surface proteins, including integrins, lectins and tetraspanins. Understanding the adapting molecular mechanisms controlling DC migration in immunity provides the basis for therapeutic interventions to dampen immune activation in autoimmunity, or to improve anti-tumour immune responses.

Topics: Animals; Antigen Presentation; Cell Communication; Cell Movement; Chemokines; Cytoskeleton; Dendritic Cells; Humans; Membrane Proteins; Mice; Neoplasms

PubMed: 32451606
DOI: 10.1007/s00430-020-00680-4

Review

Authors: Sarah Puhr, Jaeyop Lee, Ekaterina Zvezdova...

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

Review

Authors: Lili Wu, Ziqi Yan, Yiyang Jiang...

Dendritic cells (DCs) are antigen-presenting cells that bridge innate and adaptive immune responses. Multiple cell types, including DCs, rely on cellular metabolism to determine their fate. DCs substantially alter cellular metabolic pathways during activation, such as oxidative phosphorylation, glycolysis, fatty acid and amino acid metabolism, which have crucial implications for their functionality. In this review, we summarize and discuss recent progress in DC metabolic studies, focusing on how metabolic reprogramming influences DC activation and functionality and the potential metabolic differences among DC subsets. Improving the understanding of the relationship between DC biology and metabolic regulation may provide promising therapeutic targets for immune-mediated inflammatory diseases.

Topics: Humans; Dendritic Cells; Glycolysis; Oxidative Phosphorylation; Immunity; Inflammation

PubMed: 36969180
DOI: 10.3389/fimmu.2023.1140749

Review

Authors: Beatris Mastelic-Gavillet, Klara Balint, Caroline Boudousquie...

With the advent of combined immunotherapies, personalized dendritic cell (DC)-based vaccination could integrate the current standard of care for the treatment of a large variety of tumors. Due to their proficiency at antigen presentation, DC are key coordinators of the innate and adaptive immune system, and have critical roles in the induction of antitumor immunity. However, despite proven immunogenicity and favorable safety profiles, DC-based immunotherapies have not succeeded at inducing significant objective clinical responses. Emerging data suggest that the combination of DC-based vaccination with other cancer therapies may fully unleash the potential of DC-based cancer vaccines and improve patient survival. In this review, we discuss the recent efforts to develop innovative personalized DC-based vaccines and their use in combined therapies, with a particular focus on ovarian cancer and the promising results of mutanome-based personalized immunotherapies.

Topics: Cancer Vaccines; Dendritic Cells; Humans; Immunotherapy; Precision Medicine

PubMed: 31031762
DOI: 10.3389/fimmu.2019.00766

Review

Authors: Elodie Segura, Sebastian Amigorena

Dendritic cells are a rare and heterogeneous population of professional antigen-presenting cells. Several murine dendritic cell subpopulations have been identified that differ in their phenotype and functional properties. In the steady state, committed dendritic cell precursors differentiate into lymphoid organ-resident dendritic cells and migratory tissue dendritic cells. During inflammation appears an additional dendritic cell subpopulation that has been termed « inflammatory dendritic cells ». Inflammatory dendritic cells differentiate in situ from monocytes recruited to the site of inflammation. Here, we discuss how mouse inflammatory dendritic cells differ from macrophages and from other dendritic cell populations. Finally, we review recent work on human inflammatory dendritic cells.

Topics: Animals; Cell Differentiation; Dendritic Cells; Humans; Inflammation; Lymphocyte Activation; Mice; Monocytes; T-Lymphocytes

PubMed: 24472461
DOI: 10.1051/medsci/20143001015

Review

Authors: Ian Nicholas Crispe

The liver is an organ in which several major pathogens evade immune clearance and achieve chronicity. How do they do it? Recent research has documented multiple mechanisms by which immune responses in the liver are biased towards tolerance. In this review, the induction of local, intrahepatic tolerance is explored from the perspective of antigen presentation. Experiments support the role not only of liver dendritic cell subsets but also of diverse subsets of unconventional antigen-presenting cells in inducing immune suppression. The literature on this topic is controversial and sometimes contradictory, making it difficult to formulate a unified model of antigen handling and T cell priming in the liver. Here I offer a critical review of the state of the art in understanding antigen presentation in the liver.

Topics: Animals; Antigen-Presenting Cells; Cell Movement; Dendritic Cells; Endothelial Cells; Hepatic Stellate Cells; Hepatocytes; Humans; Leukocytes; Liver

PubMed: 21084131
DOI: 10.1016/j.jhep.2010.10.005