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Biochemical and Biophysical Research... Jul 2020The nuclear receptors REV-ERBα and REV-ERBβ have been demonstrated to play key roles in the regulation of numerous physiological functions, such as metabolism and the...
The nuclear receptors REV-ERBα and REV-ERBβ have been demonstrated to play key roles in the regulation of numerous physiological functions, such as metabolism and the circadian rhythm. Recent studies have established the REV-ERBs' roles in immunity, including macrophage and T cell responses. In contrast, their roles in dendritic cells have not been well defined. Dendritic cells are potent antigen presenting cells, connecting microbial sensing and innate immunity to adaptive immune responses. We demonstrate that both REV-ERBα and REV-ERBβ expression is upregulated during the course of bone marrow derived dendritic cell (BMDC) differentiation. BMDCs from REV-ERBα and REV-ERBβ deficient mice showed enhanced expression of maturation markers like CD86, MHCII, and proinflammatory cytokines. Conversely, treatment of BMDCs with a REV-ERB-specific agonist, SR9009, inhibited the expression of maturation markers and proinflammatory cytokines. Our study suggests the REV-ERBs act as negative regulators of dendritic cell development and activation. These results indicate that pharmacological modulation of REV-ERB activity could be an attractive strategy to modulate DC activation status and for DC-based therapies.
Topics: Animals; Bone Marrow Cells; Dendritic Cells; Female; Gene Deletion; Gene Expression Regulation, Developmental; Male; Mice, Inbred C57BL; Nuclear Receptor Subfamily 1, Group D, Member 1; Pyrrolidines; Receptors, Cytoplasmic and Nuclear; Repressor Proteins; Thiophenes
PubMed: 32439175
DOI: 10.1016/j.bbrc.2020.05.012 -
Frontiers in Immunology 2019Dendritic cells (DCs) are key regulators of immune responses that operate at the interface between innate and adaptive immunity, and defects in DC functions contribute... (Review)
Review
Dendritic cells (DCs) are key regulators of immune responses that operate at the interface between innate and adaptive immunity, and defects in DC functions contribute to the pathogenesis of a variety of disorders. For instance, cancer evolves in the context of limited DC activity, and some autoimmune diseases are initiated by DC-dependent antigen presentation. Thus, correcting aberrant DC functions stands out as a promising therapeutic paradigm for a variety of diseases, as demonstrated by an abundant preclinical and clinical literature accumulating over the past two decades. However, the therapeutic potential of DC-targeting approaches remains to be fully exploited in the clinic. Here, we discuss the unique features of DCs that underlie the high therapeutic potential of DC-targeting strategies and critically analyze the obstacles that have prevented the full realization of this promising paradigm.
Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Autoimmune Diseases; Autoimmunity; Cancer Vaccines; Cell Communication; Cell Differentiation; Cell Plasticity; Dendritic Cells; Disease Susceptibility; Humans; Immune Tolerance; Immunity; Immunotherapy; Neoplasms; T-Lymphocytes; Treatment Outcome
PubMed: 31736936
DOI: 10.3389/fimmu.2019.02393 -
The Yale Journal of Biology and Medicine Dec 2014Dendritic cells (DC) are professional antigen-presenting cells uniquely suited for cancer immunotherapy. They induce primary immune responses, potentiate the effector... (Review)
Review
Dendritic cells (DC) are professional antigen-presenting cells uniquely suited for cancer immunotherapy. They induce primary immune responses, potentiate the effector functions of previously primed T-lymphocytes, and orchestrate communication between innate and adaptive immunity. The remarkable diversity of cytokine activation regimens, DC maturation states, and antigen-loading strategies employed in current DC-based vaccine design reflect an evolving, but incomplete, understanding of optimal DC immunobiology. In the clinical realm, existing DC-based cancer immunotherapy efforts have yielded encouraging but inconsistent results. Despite recent U.S. Federal and Drug Administration (FDA) approval of DC-based sipuleucel-T for metastatic castration-resistant prostate cancer, clinically effective DC immunotherapy as monotherapy for a majority of tumors remains a distant goal. Recent work has identified strategies that may allow for more potent "next-generation" DC vaccines. Additionally, multimodality approaches incorporating DC-based immunotherapy may improve clinical outcomes.
Topics: Cancer Vaccines; Dendritic Cells; Drug Design; Humans; Immunotherapy; Treatment Outcome
PubMed: 25506283
DOI: No ID Found -
Frontiers in Immunology 2023Dendritic cells (DCs), a class of professional antigen-presenting cells, are considered key factors in the initiation and maintenance of anti-tumor immunity due to their... (Review)
Review
Dendritic cells (DCs), a class of professional antigen-presenting cells, are considered key factors in the initiation and maintenance of anti-tumor immunity due to their powerful ability to present antigen and stimulate T-cell responses. The important role of DCs in controlling tumor growth and mediating potent anti-tumor immunity has been demonstrated in various cancer models. Accordingly, the infiltration of stimulatory DCs positively correlates with the prognosis and response to immunotherapy in a variety of solid tumors. However, accumulating evidence indicates that DCs exhibit a significantly dysfunctional state, ultimately leading to an impaired anti-tumor immune response due to the effects of the immunosuppressive tumor microenvironment (TME). Currently, numerous preclinical and clinical studies are exploring immunotherapeutic strategies to better control tumors by restoring or enhancing the activity of DCs in tumors, such as the popular DC-based vaccines. In this review, an overview of the role of DCs in controlling tumor progression is provided, followed by a summary of the current advances in understanding the mechanisms by which the TME affects the normal function of DCs, and concluding with a brief discussion of current strategies for DC-based tumor immunotherapy.
Topics: Humans; Dendritic Cells; Tumor Microenvironment; T-Lymphocytes; Neoplasms; Immunity
PubMed: 37441069
DOI: 10.3389/fimmu.2023.1213629 -
Current Opinion in Immunology Apr 2010Plasmacytoid dendritic cells (PDC) represent a distinct immune cell type specialized in direct virus recognition and rapid secretion of type I interferon. The origin and... (Review)
Review
Plasmacytoid dendritic cells (PDC) represent a distinct immune cell type specialized in direct virus recognition and rapid secretion of type I interferon. The origin and lineage affiliation of PDC have been controversial, partly because PDC show features of both lymphocytes and dendritic cells (DC). Recent studies helped elucidate the cellular and molecular basis of PDC development. In particular, the common developmental origin and genetic similarity of PDC and classical antigen-presenting DC have been established. In addition, E protein transcription factor E2-2 was shown to control lineage commitment and gene expression program of PDC. Because E proteins are essential regulators of lymphocyte development, E2-2 activity may underlie the distinct 'lymphoid' features of PDC.
Topics: Animals; Antigen-Presenting Cells; Cell Differentiation; Cell Lineage; Dendritic Cells; Gene Expression Regulation, Developmental; Humans; Interferon Type I; Lymphocytes; TCF Transcription Factors; Transcription Factor 7-Like 2 Protein
PubMed: 20144853
DOI: 10.1016/j.coi.2010.01.005 -
Journal of Immunology Research 2014In this review, we explore the role of dendritic cell subsets in the development of tissue-specific autoimmune diseases. From the increasing list of dendritic cell... (Review)
Review
In this review, we explore the role of dendritic cell subsets in the development of tissue-specific autoimmune diseases. From the increasing list of dendritic cell subclasses, it is becoming clear that we are only at the beginning of understanding the role of these antigen presenting cells in mediating autoimmunity. Emerging research areas for the study of dendritic cell involvement in the onset and inhibition of tissue-specific autoimmunity are presented. Further, we compare tissue specific to systemic autoimmunity to demonstrate how development of dendritic cell-based therapies may be broadly applicable to both classes of autoimmunity. Continued development of these research areas will lead us closer to clinical assessment of novel immunosuppressive therapy for the reversal and prevention of tissue-specific autoimmunity. Through description of dendritic cell functions in the modulation of tissue-specific autoimmunity, we hope to stimulate a greater appreciation and understanding of the role dendritic cells play in the development and treatment of autoimmunity.
Topics: Adaptive Immunity; Autoimmune Diseases; Autoimmunity; Cell Lineage; Cell- and Tissue-Based Therapy; Dendritic Cells; Genetic Therapy; Humans; Immunity, Innate; Immunologic Factors; Organ Specificity
PubMed: 24877157
DOI: 10.1155/2014/857143 -
Human Vaccines & Immunotherapeutics Mar 2016Dendritic cells (DCs) are known to be a set of morphology, structure and function of heterogeneous professional antigen presenting cells (APCs), as well as the strongest...
Dendritic cells (DCs) are known to be a set of morphology, structure and function of heterogeneous professional antigen presenting cells (APCs), as well as the strongest functional antigen presenting cells, which can absorb, process and present antigens. As the key regulators of innate and adaptive immune responses, DCs are at the center of the immune system and capable of interacting with both B cells and T cells, thereby manipulating the humoral and cellular immune responses. DCs provide an essential link between the innate and adaptive immunity, and the strong immune activation function of DCs and their properties of natural adjuvants, make them a valuable target for antigen delivery. Targeting antigens to DC-specific endocytic receptors in combination with the relevant antibodies or ligands along with immunostimulatory adjuvants has been recently recognized as a promising strategy for designing an effective vaccine that elicits a strong and durable T cell response against intracellular pathogens and cancer. This opinion article provides a brief summary of the rationales, superiorities and challenges of existing DC-targeting approaches.
Topics: Adaptive Immunity; Animals; Antigen Presentation; Dendritic Cells; Humans; Immunity, Innate; T-Lymphocytes; Vaccines
PubMed: 26513200
DOI: 10.1080/21645515.2015.1105415 -
Immunology Aug 2011Dendritic cells (DCs) are professional antigen-presenting cells that are critical for induction of adaptive immunity and tolerance. Traditionally DCs have been divided... (Review)
Review
Dendritic cells (DCs) are professional antigen-presenting cells that are critical for induction of adaptive immunity and tolerance. Traditionally DCs have been divided into two discrete subtypes, which comprise conventional and non-conventional DCs. They are distributed across various organs in the body and comprise a heterogeneous population, which has been shown to display differences in terms of surface marker expression, function and origins. Recent studies have shed new light on the process of DC differentiation and distribution of DC subtypes in various organs. Although monocytes, macrophages and DCs share a common macrophage-DC progenitor, a common DC progenitor population has been identified that exclusively gives rise to DCs and not monocytes or macrophages. In this review, we discuss the recent advances in our understanding of DC differentiation and subtypes and provide a comprehensive overview of various DC subtypes with emphasis on their function and origins. Furthermore, in light of recent developments in the field of DC biology, we classify DCs based on the precursor populations from which the various DC subsets originate. We classify DCs derived from common DC progenitor and pre-DC populations as conventional DCs, which includes both migratory and lymphoid-resident DC subsets and classify monocyte-derived DCs and plasmacytoid DCs as non-conventional DCs.
Topics: Animals; Cell Differentiation; Dendritic Cells; Humans; Immune System
PubMed: 21627652
DOI: 10.1111/j.1365-2567.2011.03457.x -
Gut Microbes Dec 2023Aging is an inevitable natural process that impacts every individual, and understanding its effect on the gut microbiome and dendritic cell (DC) functionality in elderly... (Review)
Review
Aging is an inevitable natural process that impacts every individual, and understanding its effect on the gut microbiome and dendritic cell (DC) functionality in elderly subjects is crucial. DCs are vital antigen-presenting cells (APCs) that orchestrate the immune response, maintaining immune tolerance to self-antigens and bridging innate and adaptive immunity. With aging, there is a shift toward nonspecific innate immunity, resulting in a decline in adaptive immune responses. This alteration raises significant concerns about managing the health of an elderly population. However, the precise impact of aging and microbiome changes on DC function and their implications in lung-associated diseases remain relatively understudied. To illuminate this subject, we will discuss recent advancements in understanding the connections between aging, gut dysbiosis, DCs, and lung diseases. Emphasizing the key concepts linking age-related gut microbiome changes and DC functions, we will focus on their relevance to overall health and immune response in elderly individuals. This article aims to improve our understanding of the intricate relationship between aging, gut microbiome, and DCs, potentially benefiting the management of age-associated diseases and promoting healthy aging.
Topics: Aged; Humans; Dysbiosis; Gastrointestinal Microbiome; Immunity, Innate; Lung Diseases; Dendritic Cells
PubMed: 38087439
DOI: 10.1080/19490976.2023.2290643 -
Cellular and Molecular Life Sciences :... Jul 2016Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disorder of the central nervous system characterized by infiltration of immune cells and... (Review)
Review
Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disorder of the central nervous system characterized by infiltration of immune cells and progressive damage to myelin sheaths and neurons. There is still no cure for the disease, but drug regimens can reduce the frequency of relapses and slightly delay progression. Myeloid cells or antigen-presenting cells (APCs) such as dendritic cells (DC), macrophages, and resident microglia, are key players in both mediating immune responses and inducing immune tolerance. Mounting evidence indicates a contribution of these myeloid cells to the pathogenesis of multiple sclerosis and to the effects of treatment, the understanding of which might provide strategies for more potent novel therapeutic interventions. Here, we review recent insights into the role of APCs, with specific focus on DCs in the modulation of neuroinflammation in MS.
Topics: Animals; Antigen-Presenting Cells; Dendritic Cells; Drug Discovery; Encephalomyelitis, Autoimmune, Experimental; Humans; Immune Tolerance; Microglia; Molecular Targeted Therapy; Multiple Sclerosis
PubMed: 26970979
DOI: 10.1007/s00018-016-2170-9