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Frontiers in Immunology 2023Dendritic cells (DCs) play crucial roles in the pathogenesis of rheumatoid arthritis (RA), a prototypic autoimmune disease characterized by chronic synovitis and joint... (Review)
Review
Dendritic cells (DCs) play crucial roles in the pathogenesis of rheumatoid arthritis (RA), a prototypic autoimmune disease characterized by chronic synovitis and joint destruction. Conventional dendritic cells (cDCs) with professional antigen-presenting functions are enriched in the RA synovium. In the synovium, the cDCs are activated and show both enhanced migratory capacities and T cell activation in comparison with peripheral blood cDCs. Plasmacytoid dendritic cells, another subtype of DCs capable of type I interferon production, are likely to be tolerogenic in RA. Monocyte-derived dendritic cells (moDCs), once called "inflammatory DCs", are localized in the RA synovium, and they induce T-helper 17 cell expansion and enhanced proinflammatory cytokine production. Recent studies revealed that synovial proinflammatory hypoxic environments are linked to metabolic reprogramming. Activation of cDCs in the RA synovium is accompanied by enhanced glycolysis and anabolism. In sharp contrast, promoting catabolism can induce tolerogenic DCs from monocytes. Herein, we review recent studies that address the roles of DCs and their immunometabolic features in RA. Immunometabolism of DCs could be a potential therapeutic target in RA.
Topics: Humans; Arthritis, Rheumatoid; Synovial Membrane; Autoimmune Diseases; Monocytes; Dendritic Cells
PubMed: 37251399
DOI: 10.3389/fimmu.2023.1161148 -
Immunology Letters Jan 2023The gut comprises the largest body interface with the environment and is continuously exposed to nutrients, food antigens, and commensal microbes, as well as to harmful... (Review)
Review
The gut comprises the largest body interface with the environment and is continuously exposed to nutrients, food antigens, and commensal microbes, as well as to harmful pathogens. Subsets of both macrophages and dendritic cells (DCs) are present throughout the intestinal tract, where they primarily inhabit the gut-associate lymphoid tissue (GALT), such as Peyer's patches and isolated lymphoid follicles. In addition to their role in taking up and presenting antigens, macrophages and DCs possess extensive functional plasticity and these cells play complementary roles in maintaining immune homeostasis in the gut by preventing aberrant immune responses to harmless antigens and microbes and by promoting host defense against pathogens. The ability of macrophages and DCs to induce either inflammation or tolerance is partially lineage imprinted, but can also be dictated by their activation state, which in turn is determined by their specific microenvironment. These cells express several surface and intracellular receptors that detect danger signals, nutrients, and hormones, which can affect their activation state. DCs and macrophages play a fundamental role in regulating T cells and their effector functions. Thus, modulation of intestinal mucosa immunity by targeting antigen presenting cells can provide a promising approach for controlling pathological inflammation. In this review, we provide an overview on the characteristics, functions, and origins of intestinal macrophages and DCs, highlighting the intestinal microenvironmental factors that influence their functions during homeostasis. Unraveling the mechanisms by which macrophages and DCs regulate intestinal immunity will deepen our understanding on how the immune system integrates endogenous and exogenous signals in order to maintain the host's homeostasis.
Topics: Humans; Macrophages; Lymphoid Tissue; Inflammation; Allergens; Dendritic Cells; Intestinal Mucosa
PubMed: 36623708
DOI: 10.1016/j.imlet.2023.01.003 -
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 Immunology Jul 2023Since their discovery, the identity of plasmacytoid dendritic cells (pDCs) has been at the center of a continuous dispute in the field, and their classification as... (Review)
Review
Since their discovery, the identity of plasmacytoid dendritic cells (pDCs) has been at the center of a continuous dispute in the field, and their classification as dendritic cells (DCs) has been recently re-challenged. pDCs are different enough from the rest of the DC family members to be considered a lineage of cells on their own. Unlike the exclusive myeloid ontogeny of cDCs, pDCs may have dual origin developing from myeloid and lymphoid progenitors. Moreover, pDCs have the unique ability to quickly secrete abundant levels of type I interferon (IFN-I) in response to viral infections. In addition, pDCs undergo a differentiation process after pathogen recognition that allows them to activate T cells, a feature that has been shown to be independent of presumed contaminating cells. Here, we aim to provide an overview of the historic and current understanding of pDCs and argue that their classification as either lymphoid or myeloid may be an oversimplification. Instead, we propose that the capacity of pDCs to link the innate and adaptive immune response by directly sensing pathogens and activating adaptive immune responses justify their inclusion within the DC network.
Topics: Adaptive Immunity; Cell Differentiation; Dendritic Cells; Immunity, Humoral; T-Lymphocytes
PubMed: 37269733
DOI: 10.1016/j.molimm.2023.05.007 -
Frontiers in Immunology 2022Dendritic cells (DC) are uniquely capable of initiating and directing immune responses. The range of their activities grounds in the heterogeneity of DC subsets and... (Review)
Review
Dendritic cells (DC) are uniquely capable of initiating and directing immune responses. The range of their activities grounds in the heterogeneity of DC subsets and their functional plasticity. Numerical and functional DC changes influence the development and progression of disease, and correction of such dysregulations has the potential to treat disease causally. In this review, we discuss the major advances in our understanding of the regulation of DC lineage formation, differentiation, and function in the skin. We describe the alteration of DC in disease as well as possibilities for therapeutic reprogramming with a focus on tolerogenic DC. Because regulatory T cells (Treg) are indispensable partners of DC in the induction and control of tolerance, we pay special attention to the interactions with these cells. Above all, we would like to arouse fascination for this cell type and its therapeutic potential in skin diseases.
Topics: Cell Differentiation; Dendritic Cells; Immune Tolerance; Skin; T-Lymphocytes, Regulatory
PubMed: 35837386
DOI: 10.3389/fimmu.2022.929000 -
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 -
Frontiers in Cellular and Infection... 2020The fungal pathogen can cause life-threatening infections in immune compromised individuals. This pathogen is typically acquired via inhalation, and enters the... (Review)
Review
The fungal pathogen can cause life-threatening infections in immune compromised individuals. This pathogen is typically acquired via inhalation, and enters the respiratory tract. Innate immune cells such as macrophages and dendritic cells (DCs) are the first host cells that encounter , and the interactions between and innate immune cells play a critical role in the progression of disease. possesses several virulence factors and evasion strategies to prevent its killing and destruction by pulmonary phagocytes, but these phagocytic cells can also contribute to anti-cryptococcal responses. This review will focus on the interactions between and primary macrophages and dendritic cells (DCs), dealing specifically with the cryptococcal/pulmonary cell interface.
Topics: Cryptococcosis; Cryptococcus neoformans; Dendritic Cells; Humans; Macrophages; Macrophages, Alveolar
PubMed: 32117810
DOI: 10.3389/fcimb.2020.00037 -
Frontiers in Immunology 2023Dendritic cells (DCs) are sentinel immune cells that form a critical bridge linking the innate and adaptive immune systems. Extensive research addressing the cellular... (Review)
Review
Dendritic cells (DCs) are sentinel immune cells that form a critical bridge linking the innate and adaptive immune systems. Extensive research addressing the cellular origin and heterogeneity of the DC network has revealed the essential role played by the spatiotemporal activity of key transcription factors. In response to environmental signals DC mature but it is only following the sensing of environmental signals that DC can induce an antigen specific T cell response. Thus, whilst the coordinate action of transcription factors governs DC differentiation, sensing of environmental signals by DC is instrumental in shaping their functional properties. In this review, we provide an overview that focuses on recent advances in understanding the transcriptional networks that regulate the development of the reported DC subsets, shedding light on the function of different DC subsets. Specifically, we discuss the emerging knowledge on the heterogeneity of cDC2s, the ontogeny of pDCs, and the newly described DC subset, DC3. Additionally, we examine critical transcription factors such as IRF8, PU.1, and E2-2 and their regulatory mechanisms and downstream targets. We highlight the complex interplay between these transcription factors, which shape the DC transcriptome and influence their function in response to environmental stimuli. The information presented in this review provides essential insights into the regulation of DC development and function, which might have implications for developing novel therapeutic strategies for immune-related diseases.
Topics: Gene Expression Regulation; Cell Differentiation; Transcriptome; Dendritic Cells
PubMed: 37520521
DOI: 10.3389/fimmu.2023.1182553 -
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 Leukocyte Biology Jul 2023Allergic asthma is a chronic inflammatory disease characterized by Th2, conventional dendritic cell, and B-cell activation. In addition to excessive inflammation, asthma...
Allergic asthma is a chronic inflammatory disease characterized by Th2, conventional dendritic cell, and B-cell activation. In addition to excessive inflammation, asthma pathogenesis includes dysregulation of anti-inflammatory pathways, such as the CD200/CD200R pathway. Thus, we investigated whether a CD200R agonist, CD200Fc, could disrupt the inflammatory cascade in chronic allergic asthma pathogenesis using a mice model of experimental asthma. Mice were exposed to house dust mites for 5 wk, and CD200Fc treatment was initiated after chronic inflammation was established (starting on week 4). We demonstrate that chronic house dust mite exposure altered CD200 and CD200R expression on lung immune cell populations, including upregulation of CD200 on alveolar macrophages and reduced expression of CD200 on conventional dendritic cells. CD200Fc treatment does not change bronchoalveolar cellular infiltration, but it attenuates B-cell activation and skews the circulating immunoglobulin profile toward IgG2a. This is accompanied by reduced activation of conventional dendritic cells, including lower expression of CD40, especially on conventional dendritic cell subset 2 CD200R+. Furthermore, we confirm that CD200Fc can directly modulate conventional dendritic cell activation in vitro using bone marrow-derived dendritic cells. Thus, the CD200/CD200R pathway is dysregulated during chronic asthma pathogenesis, and the CD200R agonist modulates B-cell and dendritic cell activation but, in our chronic model, is not sufficient to alter inflammation measured in bronchoalveolar lavage.
Topics: Mice; Animals; Pyroglyphidae; Asthma; Inflammation; Allergens; Dendritic Cells
PubMed: 37032534
DOI: 10.1093/jleuko/qiad042