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Frontiers in Immunology 2020
Topics: Dendritic Cells; Humans; Immunotherapy; Neoplasms
PubMed: 32296426
DOI: 10.3389/fimmu.2020.00507 -
Immunity Jun 2023Early-life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here, we...
Early-life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here, we showed that tolerance in skin was controlled by microbial interaction with a specialized subset of antigen-presenting cells. More particularly, CD301b type 2 conventional dendritic cells (DCs) in neonatal skin were specifically capable of uptake and presentation of commensal antigens for the generation of regulatory T (Treg) cells. CD301b DC2 were enriched for phagocytosis and maturation programs, while also expressing tolerogenic markers. In both human and murine skin, these signatures were reinforced by microbial uptake. In contrast to their adult counterparts or other early-life DC subsets, neonatal CD301b DC2 highly expressed the retinoic-acid-producing enzyme, RALDH2, the deletion of which limited commensal-specific Treg cell generation. Thus, synergistic interactions between bacteria and a specialized DC subset critically support early-life tolerance at the cutaneous interface.
Topics: Animals; Mice; Humans; Skin; Dendritic Cells; T-Lymphocytes, Regulatory; Immune Tolerance; Aldehyde Oxidoreductases
PubMed: 37028427
DOI: 10.1016/j.immuni.2023.03.008 -
Trends in Immunology Feb 2023In contrast to conventional dendritic cells (cDCs) that are constantly exposed to microbial signals at anatomical barriers, cDCs in systemic lymphoid organs are... (Review)
Review
In contrast to conventional dendritic cells (cDCs) that are constantly exposed to microbial signals at anatomical barriers, cDCs in systemic lymphoid organs are sheltered from proinflammatory stimulation in the steady state but respond to inflammatory signals by gaining specific immune functions in a process referred to as maturation. Recent findings show that, during maturation, a population of systemic tolerogenic cDCs undergoes an acute tumor necrosis factor α (TNFα)-mediated cell death, resulting in the loss of tolerance-inducing capacity. This tolerogenic cDC population is restored upon return to the homeostatic baseline. We propose that such a dynamic reshaping of cDC populations becomes the foundation of a novel framework for maintaining tolerance at the steady state while being conducive to unhampered initiation of immune responses under proinflammatory conditions.
Topics: Humans; Immune Tolerance; Dendritic Cells
PubMed: 36599743
DOI: 10.1016/j.it.2022.12.006 -
Frontiers in Immunology 2022The lungs are constantly exposed to environmental and infectious agents such as dust, viruses, fungi, and bacteria that invade the lungs upon breathing. The lungs are... (Review)
Review
The lungs are constantly exposed to environmental and infectious agents such as dust, viruses, fungi, and bacteria that invade the lungs upon breathing. The lungs are equipped with an immune defense mechanism that involves a wide variety of immunological cells to eliminate these agents. Various types of dendritic cells (DCs) and macrophages (MACs) function as professional antigen-presenting cells (APCs) that engulf pathogens through endocytosis or phagocytosis and degrade proteins derived from them into peptide fragments. During this process, DCs and MACs present the peptides on their major histocompatibility complex class I (MHC-I) or MHC-II protein complex to naïve CD8 or CD4 T cells, respectively. In addition to these cells, recent evidence supports that antigen-specific effector and memory T cells are activated by other lung cells such as endothelial cells, epithelial cells, and monocytes through antigen presentation. In this review, we summarize the molecular mechanisms of antigen presentation by APCs in the lungs and their contribution to immune response.
Topics: Antigen Presentation; Cells, Cultured; Dendritic Cells; Endothelial Cells; Lung
PubMed: 35615351
DOI: 10.3389/fimmu.2022.860915 -
International Journal of Molecular... Jun 2022Dendritic cells mediate innate and adaptive immune responses and are directly involved in the activation of cytotoxic T lymphocytes that kill tumor cells. Dendritic... (Review)
Review
Dendritic cells mediate innate and adaptive immune responses and are directly involved in the activation of cytotoxic T lymphocytes that kill tumor cells. Dendritic cell-based cancer immunotherapy has clinical benefits. Dendritic cell subsets are diverse, and tumors can be hot or cold, depending on their immunogenicity; this heterogeneity affects the success of dendritic cell-based immunotherapy. Here, we review the ontogeny of dendritic cells and dendritic cell subsets. We also review the characteristics of hot and cold tumors and briefly introduce therapeutic trials related to hot and cold tumors. Lastly, we discuss dendritic cell-based cancer immunotherapy in hot and cold tumors.
Topics: Dendritic Cells; Humans; Immunotherapy; Neoplasms; T-Lymphocytes, Cytotoxic
PubMed: 35806328
DOI: 10.3390/ijms23137325 -
Current Opinion in Immunology Jun 2020The skin is inhabited by several immune cell populations that serve as a first line of defence against pathogen invasion. Amongst these populations are dendritic cells,... (Review)
Review
The skin is inhabited by several immune cell populations that serve as a first line of defence against pathogen invasion. Amongst these populations are dendritic cells, which play an essential sentinel function by taking up antigen or infectious agents and transporting them to the lymph node for T cell recognition and the priming of immune responses. In this review, we briefly summarise recent advances showing how skin dendritic cells are connected to a network of epithelial and stromal cells, which provide structural support, growth factors, spatial cues, contact with the external environment and the skin microbiome, and favour interactions with other immune cells. We propose that this network creates a unique skin environment that may condition dendritic cell phenotype and function.
Topics: Dendritic Cells; Humans; Langerhans Cells; Lymph Nodes; Microbiota; Skin
PubMed: 32387901
DOI: 10.1016/j.coi.2020.03.006 -
Nature Materials Nov 2020
Topics: Cell Movement; Cell Tracking; Dendritic Cells
PubMed: 33082569
DOI: 10.1038/s41563-020-00828-w -
Immunology Letters Apr 2021
Topics: Adjuvants, Immunologic; Biomarkers; Cytokines; Dendritic Cells; Humans; Immune System; Immunologic Factors
PubMed: 33609612
DOI: 10.1016/j.imlet.2021.02.004 -
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 -
The Journal of Clinical Investigation Feb 2023Antigen presentation machinery and professional antigen-presenting cells (APCs) are fundamental for an efficacious immune response against cancers, especially in the... (Review)
Review
Antigen presentation machinery and professional antigen-presenting cells (APCs) are fundamental for an efficacious immune response against cancers, especially in the context of T cell-centric immunotherapy. Dendritic cells (DCs), the gold standard APCs, play a crucial role in initiating and maintaining a productive antigen-specific adaptive immunity. In recent decades, ex vivo-differentiated DCs from circulating CD14+ monocytes have become the reference for APC-based immunotherapy. DCs loaded with tumor-associated antigens, synthetic peptides, or RNA activate T cells with antitumor properties. This strategy has paved the way for the development of alternative antigen-presenting vaccination strategies, such as monocytes, B cells, and artificial APCs, that have shown effective therapeutic outcomes in preclinical cancer models. The search for alternative APC platforms was initiated by the overall limited clinical impact of DC vaccines, especially in indications such as gliomas, a primary brain tumor known for resistance to any immune intervention. In this Review, we navigate the APC immune therapeutics' past, present, and future in the context of primary brain tumors.
Topics: Humans; Dendritic Cells; Antigen Presentation; T-Lymphocytes; Glioma; Immunotherapy; Cancer Vaccines
PubMed: 36719372
DOI: 10.1172/JCI163449