Understanding Of Dendritic Cells Research Articles

A primer on single-cell RNA-seq analysis using dendritic cells as a case study.

Recent advances in single-cell (sc) transcriptomics have revolutionized our understanding of dendritic cells (DCs), pivotal players of the immune system. ScRNA-sequencing (scRNA-seq) has unraveled a previously unrecognized complexity and heterogeneity of DC subsets, shedding light on their ontogeny and specialized roles. However, navigating the rapid technological progress and computational methods can be daunting for researchers unfamiliar with the field. This review aims to provide immunologists with a comprehensive introduction to sc transcriptomic analysis, offering insights into recent developments in DC biology. Addressing common analytical queries, we guide readers through popular tools and methodologies, supplemented with references to benchmarks and tutorials for in-depth understanding. By examining findings from pioneering studies, we illustrate how computational techniques have expanded our knowledge of DC biology. Through this synthesis, we aim to equip researchers with the necessary tools and knowledge to navigate and leverage scRNA-seq for unraveling the intricacies of DC biology and advancing immunological research.

Intracellular Monitoring by Dendritic Cells – a New Way to Stay Informed – From Simple Scavenger to Active Gatherer.

Abstract The ability of dendritic cells (DCs) to acquire antigen from their environment is critical for the induction of an adaptive immune response and the maintenance of tolerance. Despite its importance, it is tacitly assumed that DCs acquire antigen by scavenging extracellular material via endocytosis or macropinocytosis. Here, using labeled RNA and time lapse imaging, we observe DCs siphoning material directly from live neighboring keratinocytes. This contact dependent mechanism of antigen uptake – which we term intracellular monitoring– accounts for a large percentage of RNA transferred to DCs, and cannot be blocked by inhibitors of known antigen uptake processes. It is exclusive to DCs, as other cell types do not efficiently siphon RNA from neighboring cells, and common among most DCs subsets tested. Langerhans cells with a conditional gene deletion can successfully overcome their deficiency by siphoning RNA and protein from their neighbors, but only if the deleted protein is expressed in the donating cell. Such behavior reframes our understanding of DCs from mere scavengers to highly informed supervisors with extensive access to the cytosol of surrounding cells. Intracellular monitoring may therefore play important roles in the maintenance of tolerance, defense against infection, and detection of cancerous cells.

A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections.

Dendritic cells (DC) connect the innate and adaptive arms of the immune system and carry out numerous roles that are significant in the context of viral disease. Their functions include the control of inflammatory responses, the promotion of tolerance, cross-presentation, immune cell recruitment and the production of antiviral cytokines. Based primarily on the available literature that characterizes the behaviour of many DC subsets during Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), we speculated possible mechanisms through which DC could contribute to COVID-19 immune responses, such as dissemination of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to lymph nodes, mounting dysfunctional inteferon responses and T cell immunity in patients. We highlighted gaps of knowledge in our understanding of DC in COVID-19 pathogenesis and discussed current pre-clinical development of therapies for COVID-19.

Linking immune responses with fibrosis in allergic eye disease.

Here, we explore an emerging theme in the literature, which is the role of dendritic cells in the causation of fibrosis. To fully appreciate this pathway to disease, we also review the most recent literature regarding dendritic cell biology as it pertains to ocular surface tissues. On the basis of this information, we propose a unifying hypothesis for how dendritic cells may cause conjunctival fibrosis in the allergy setting. Work in models of airway remodeling and liver fibrosis has pointed to a potentially central role for dendritic cells in the pathobiology of fibrosis. Indeed, these cells are recognized as the most potent antigen-presenting cells, and as such activate T lymphocytes that are profibrotic under certain conditions. However, recent findings suggest a more direct role for dendritic cells, which opens up the possibility that a similar pathway may be relevant in the causation of conjunctival fibrosis, particularly in allergic eye disease. Conjunctival fibrosis is a serious clinical concern and is associated with chronic inflammation of the ocular surface tissue, such as in allergic eye disease. Dendritic cells are required in mediating allergic disease by activating pathologic T lymphocytes. Recent findings pointing to a central role for dendritic cell in fibrosis may, however, mean that these cells could also be contributing directly to conjunctival fibrosis. If so, furthering our understanding of dendritic cells could lead to the identification of novel and more effective therapeutic strategies to treat this disease.

Inclusive estimation of complex antigen presentation functions of monocyte-derived dendritic cells differentiated under normoxia and hypoxia conditions.

Dendritic cells (DCs) generated from monocytes under 20% O2 are now used as therapeutic tools for cancer patients. However, the O2 concentration is between 3 and 0.5% in most tissues. We evaluated these complicated functions of DCs under oxygen tensions mimicking in vivo situations. Immature DCs (imDCs) were generated from monocytes using IL-4 and GM-CSF under normoxia (20% O2; N-imDCs) or hypoxia (1% O2; H-imDCs). Mature DCs (mDCs) were induced with LPS. DCs were further exposed to normoxia (N/N-DCs) or hypoxia (N/H-DCs and H/H-DCs) conditions. Using a 2-D culture system, H-DCs were smaller in size than N-DCs, and H/H-DCs exhibited higher allo-T cell stimulation ability than N/N-DCs and N/H-DCs. On the other hand, motility and phagocytic ability of H/H-DCs were significantly lower than those of N/H-DCs and N/N-DCs. In a 3-D culture system, however, maturation of H/H-imDCs and N/H-imDCs was suppressed compared with N/N-imDCs as a result of their decreased motility and phagocytosis. Interestingly, silencing of HIF-1α by RNA interference decreased CD83 expression without affecting any antigen presentation abilities except for the ability to stimulate the allo-T cell population. Our data could help our understanding of DCs, especially therapeutic DCs, in vivo.

Dendritic cells: a family portrait at mid‐gestation

Recent advances in our understanding of dendritic cells (DCs) and their role in tolerance and immunity has fuelled study of their normal development and function within the reproductive tract. The common hypothesis that pregnancy is a state of immune suppression or deviation now includes the idea that alterations in DC phenotype and function are critical for maternal tolerance. We chose to study DCs in the uterus and lymphoid tissue in non-pregnant and pregnant mice at mid-gestation to understand what DC-related factors may be involved in premature birth. We used a mouse model where the mother's immune system has been shown to respond to the male antigen H-Y. Observed differences among DCs in the uterus, uterine draining nodes and spleen, even in non-pregnant mice, suggest the existence of a specialized uterus-specific subset of DCs. We further found that, amongst CD45(+) CD11c(+) cells in the uterus and peripheral lymphoid tissue of pregnant mice, expression of major histocompatibility complex class II (MHC II) and costimulatory molecules (i.e. CD80) was similar to that in the non-pregnant state. Moreover, there was no pregnancy-related decrease in the proportion of CD11c(+) cells in the uterus or in the uterine node that were CD11b(-) CD8(+). Pregnancy increased the CD11b(+) subsets and the expression of chemokine (C-C motif) ligand 6 (CCL6) in DCs of the uterine draining nodes. Finally, DC subsets showed variable expression, with respect to tissue and pregnancy, of the cytokine interleukin-15, which is important in lymphoid cell homeostasis. For DCs, pregnancy is not a state of immune paralysis, but of dynamic developmental change.

Getting together: Dendritic cells, T cells, collaboration and fates

Getting together: Dendritic cells, T cells, collaboration and fates

Pathogen-Related Signal Transduction Pathways of Dendritic Cells: Perspectives for Cancer Immunotherapy

Dendritic cells (DCs) play a crucial role in translating innate to adaptive immunity. DC-based cancer immunotherapy has been under evaluation; however, its clinical benefits remain limited. A better understanding of DCs is, therefore, needed to improve clinical outcomes. Toll-like receptors (TLRs) were initially identified as molecules that recognize and bind pathogen-associated molecular patterns (PAMPs) leading to DC maturation. The TLR signaling pathway leads to the activation of NF-κB, which initiates the transcription of proinflammatory cytokine genes. As the sensors of RNA viruses in the cellular cytoplasm, RNA helicases containing retinoic acidinducible gene-I (RIG-I) have been shown to recognize the viral RNA genome, and recent studies have demonstrated that these helicases strongly induce the upregulation of type I interferons. We recently demonstrated that RNA viruses strongly activated DCs, and this finding is expected to aid in the development of improved DC-based cancer immunotherapy. We then proposed DC-based “immunostimulatory RNA virotherapy” as a novel therapeutic approach. The janus kinases (JAKs) and the signal transducers and activators of transcription (STATs) are key molecules in a major signaling pathway for modulating DC function; suppressors of cytokine signaling (SOCSs) inhibit this pathway. Some recent studies have suggested that the suppression of SOCS family proteins in DCs modulates immune responses, including anticancer immunity. Here, we review recent progress in the elucidation of the mechanisms of signal transduction pathways in DCs; it is hoped that such investigations will eventually lead to a variety of DC-based cancer immunotherapies.

Enhancing DNA vaccine potency by modifying the properties of antigen-presenting cells

DNA vaccines represent a potentially promising approach for antigen-specific immunotherapy. Advances in our knowledge of the adaptive immune system have indicated that professional antigen-presenting cells, especially dendritic cells (DCs), play a key role in the generation of antigen-specific immune responses. Thus, the modification of the properties of DCs represents an important strategy for enhancing the potency of DNA vaccines. This review discusses strategies to increase the number of antigen-expressing DCs, enhance antigen expression, processing and presentation in DCs, promote the activation and function of DCs, and improve DC and T-cell interaction, in order to optimize DNA vaccine-elicited immune responses. Continuing progress in our understanding of DC and T-cell biology serves as a foundation for further improvement of DNA vaccine potency, which may lead to future clinical applications of DNA vaccines for the control of infectious diseases and malignancies.

Dendritic Cells and CD4+CD25+ T Regulatory Cells: Crosstalk Between Two Professionals in Immunity versus Tolerance

Dendritic cells (DCs) are professional antigen presenting cells (APCs). (CD4+)CD25+ T regulatory cells (T regs) are recognized as professional regulatory cells. DCs not only initiate T cell immunity by uptake, processing and presentation of specific antigens, but also induce immune tolerance by deletion of T cells and/or induction of regulatory T cells. (CD4+)CD25+ T regs maintain immune tolerance by suppressing the function of CD4+ and CD8+ T cells, B cells, macrophages, DCs and NK cells. It would be inconceivable that the delicate balance between immunity and tolerance could be kept impeccable without the crosstalk between DCs and (CD4+)CD25+ T regs. This review focuses on the recent development in our understanding of DCs and (CD4+)CD25+ T regs in immune tolerance, with transforming growth factor-beta (TGF-beta) serving as a potential link between these two professionals.

Dendritic cells and HNSCC: A potential treatment option? (Review)

Patient survival in head and neck squamous cell cancer (HNSCC) has not changed significantly in many years, despite progress in surgical, radiotherapy and chemotherapy techniques. Immunotherapy, a rapidly progressing alternative cancer treatment, aims to prompt or assist the body's immune system to combat the disease itself. A number of strategies exist including the use of dendritic cells, natural antigen presenting cells capable of stimulating an anti-tumor immune response. Encouraging work has been performed using these cells as vaccines against a number of tumors especially melanoma. Work with head and neck cancer is also encouraging, but less advanced. Dendritic cell presence in head and neck squamous cell cancers is associated with an improved prognosis, however due to immunosuppression, the exact mechanism of which remains poorly understood, these cells do not function efficiently. This prevents the stimulation of an effective anti-tumor immune response by the patient and allows tumor growth to continue. This review summarises the current level of understanding of dendritic cells and their relationship with HNSCC. It briefly summarises work with dendritic cells and other cancers where relevant to HNSCC; dendritic cells and head and neck cancer; the possible causes of dendritic cell impairment; the techniques used to restore their function and the methods used to prime the dendritic cells prior to their use as vaccines for the stimulation of an anti-tumor response.