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International Journal of Molecular... Dec 2023Allergic rhinitis (AR) is a common pathological condition in otorhinolaryngology. Its prevalence has been increasing worldwide and is becoming a major burden to the... (Review)
Review
Allergic rhinitis (AR) is a common pathological condition in otorhinolaryngology. Its prevalence has been increasing worldwide and is becoming a major burden to the world population. Dendritic cells (DCs) are typically activated and matured after capturing, phagocytosing, and processing allergens during the immunopathogenesis of AR. In addition, the process of DC activation and maturation is accompanied by the production of exosomes, which are cell‑derived extracellular vesicles (EVs) that can carry proteins, lipids, nucleic acids, and other cargoes involved in intercellular communication and material transfer. In particular, DC‑derived exosomes (Dex) can participate in allergic immune responses, where the biological substances carried by them can have potentially important implications for both the pathogenesis and treatment of AR. Dex can also be exploited to carry anti‑allergy agents to effectively treat AR. This provides a novel method to explore the pathogenesis of and treatment strategies for AR further. Therefore, the present review focuses on the origin, composition, function, and biological characteristics of DCs, exosomes, and Dex, in addition to the possible relationship between Dex and AR.
Topics: Humans; Exosomes; Rhinitis, Allergic; Allergens; Extracellular Vesicles; Dendritic Cells
PubMed: 37888754
DOI: 10.3892/ijmm.2023.5320 -
Advanced Science (Weinheim,... Nov 2023Spleen and lymphoid organs are important targets for messenger RNA (mRNA) delivery in various applications. Current nanoparticle delivery methods rely on drainage to...
Spleen and lymphoid organs are important targets for messenger RNA (mRNA) delivery in various applications. Current nanoparticle delivery methods rely on drainage to lymph nodes from intramuscular or subcutaneous injections. In difficult-to-transfect antigen-presenting cells (APCs), such as dendritic cells (DCs), effective mRNA transfection remains a significant challenge. In this study, a lymphatic targeting carrier using DC membranes is developed, that efficiently migrated to lymphoid organs, such as the spleen and lymph nodes. The nanoparticles contained an ionizable lipid (YK009), which ensured a high encapsulation efficacy of mRNA and assisted mRNA with endosomal escape after cellular uptake. Dendritic cell-mimicking nanoparticles (DCMNPs) showed efficient protein expression in both the spleen and lymph nodes after intramuscular injections. Moreover, in immunized mice, DCMNP vaccination elicited Spike-specific IgG antibodies, neutralizing antibodies, and Th1-biased SARS-CoV-2-specific cellular immunity. This work presents a powerful vaccine formula using DCMNPs, which represents a promising vaccine candidate for further research and development.
Topics: Mice; Animals; Dendritic Cells; RNA, Messenger; Nanoparticles; Immunity, Cellular; Vaccines
PubMed: 37867227
DOI: 10.1002/advs.202302423 -
Current Opinion in Immunology Aug 2023Type 1 classical dendritic cells (cDC1s) have emerged as the major antigen-presenting cell performing cross-presentation (XP) in vivo, but the antigen-processing... (Review)
Review
Type 1 classical dendritic cells (cDC1s) have emerged as the major antigen-presenting cell performing cross-presentation (XP) in vivo, but the antigen-processing pathway in this cell remains obscure. Two competing models for in vivo XP of cell-associated antigens by cDC1 include a vacuolar pathway and cytosolic pathway. A vacuolar pathway relies on directing antigens captured in vesicles toward a class I major histocompatibility complex loading compartment independently of cytosolic entry. Alternate proposals invoke phagosomal rupture, either constitutive or triggered by spleen tyrosine kinase (SYK) signaling in response to C-type lectin domain family 9 member A (CLEC9A) engagement, that releases antigens into the cytosol for proteasomal degradation. The Beige and Chediak-Higashi (BEACH) protein WD repeat- and FYVE domain-containing protein 4 (WDFY4) is strictly required for XP of cell-associated antigens in vivo. However, the cellular mechanism for WDFY4 activity remains unknown and its requirement in XP in vivo is currently indifferent regarding the vacuolar versus cytosolic pathways. Here, we review the current status of these models and discuss the need for future investigation.
Topics: Humans; Cross-Priming; Antigen Presentation; Cytosol; Dendritic Cells; Antigens; Histocompatibility Antigens Class I
PubMed: 37276818
DOI: 10.1016/j.coi.2023.102350 -
Critical Reviews in Oncology/hematology Dec 2023Plasmacytoid dendritic cells (pDCs) are a specific dendritic cell type stemming from the myeloid lineage. Clinically and pathologically, neoplasms associated with pDCs... (Review)
Review
Plasmacytoid dendritic cells (pDCs) are a specific dendritic cell type stemming from the myeloid lineage. Clinically and pathologically, neoplasms associated with pDCs are classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN), mature plasmacytoid dendritic myeloid neoplasm (MPDMN) and pDC expansion in myeloid neoplasms (MNs). BPDCN was considered a rare and aggressive neoplasm in the 2016 World Health Organization (WHO) classification. MPDMN, known as mature pDC-derived neoplasm, is closely related to MNs and was first recognized in the latest 2022 WHO classification, proposing a new concept that acute myeloid leukemia cases could show clonally expanded pDCs (pDC-AML). With the advances in detection techniques, an increasing number of pDC expansion in MNs have been reported, but whether the pathogenesis is similar to that of MPDMN remains unclear. This review focuses on patient characteristics, diagnosis and treatment of pDC expansion in MNs to gain further insight into this novel and unique provisional subtype.
Topics: Humans; Leukemia, Myeloid, Acute; Immunophenotyping; Dendritic Cells; Hematologic Neoplasms; Skin Neoplasms
PubMed: 37863402
DOI: 10.1016/j.critrevonc.2023.104186 -
Cancer Biotherapy & Radiopharmaceuticals Sep 2023Dendritic cells (DCs) are the most important antigen-presenting cells in the body and play a key role in antigen recognition, uptake, processing, and presentation and... (Review)
Review
Dendritic cells (DCs) are the most important antigen-presenting cells in the body and play a key role in antigen recognition, uptake, processing, and presentation and mediate nonspecific immunity and specific immunity. To summarize the main findings that DC vaccines are a new immunotherapy scheme combining the strengths of tumor antigens and DCs that can boost the body's identification and clearance of tumors. In this review, the authors focus on the biological characteristics of DCs, recent advances in the understanding of antitumor mechanisms, and the classification of DC vaccines. The current progress of DC-based vaccine immunotherapy for common tumors with high morbidity or mortality in China were systematically summarize. The DC vaccines combining the strengths of tumor antigens will provide directions to explore reasonable, safe, and effective combination immunotherapy strategies for tumors in the future.
Topics: Humans; China; Immunotherapy; Antigens, Neoplasm; Dendritic Cells
PubMed: 37699203
DOI: 10.1089/cbr.2023.0041 -
Proceedings of the National Academy of... Dec 2023Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan...
Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt MHCII type 3 innate lymphoid cells (ILC3) have also been implicated in the instruction of microbiota-specific Tregs. While RORγt APCs have been actively investigated in mice, the identity and function of these cell subsets in humans remain elusive. Herein, we identify a rare subset of RORγt cells with dendritic cell (DC) features through integrated single-cell RNA sequencing and single-cell ATAC sequencing. These cells, which we term RORγt DC-like cells (R-DC-like), exhibit DC morphology, express the MHC class II machinery, and are distinct from all previously reported DC and ILC3 subsets, but share transcriptional and epigenetic similarities with DC2 and ILC3. We have developed procedures to isolate and expand them in vitro, enabling their functional characterization. R-DC-like cells proliferate in vitro, continue to express RORγt, and differentiate into CD1c DC2-like cells. They stimulate the proliferation of allogeneic T cells. The identification of human R-DC-like cells with proliferative potential and plasticity toward CD1c DC2-like cells will prompt further investigation into their impact on immune homeostasis, inflammation, and autoimmunity.
Topics: Humans; Mice; Animals; Lymphocytes; Immunity, Innate; Nuclear Receptor Subfamily 1, Group F, Member 3; Inflammation; Dendritic Cells
PubMed: 38109523
DOI: 10.1073/pnas.2318710120 -
European Journal of Immunology Nov 2023Dendritic cells (DCs) bridge innate and adaptive immunity. Their main function is to present antigens to prime T cells and initiate and shape adaptive responses. Antigen... (Review)
Review
Dendritic cells (DCs) bridge innate and adaptive immunity. Their main function is to present antigens to prime T cells and initiate and shape adaptive responses. Antigen presentation takes place through intimate contacts between the two cells, termed immune synapses (IS). During the formation of IS, information travels towards the T-cell side to induce and tune its activation; but it also travels in reverse via engagement of membrane receptors and within extracellular vesicles transferred to the DC. Such reverse information transfer and its consequences on DC fate have been largely neglected. Here, we review the events and effects of IS-mediated antigen presentation on DCs. In addition, we discuss novel technological advancements that enable monitoring DCs interactions with T lymphocytes, the main effects of DCs undergoing productive IS (postsynaptic DCs, or psDCs), and how reverse information transfer could be harnessed to modulate immune responses for therapeutic intervention.
Topics: Immunological Synapses; Dendritic Cells; T-Lymphocytes; Antigen Presentation; Antigens
PubMed: 37598303
DOI: 10.1002/eji.202350393 -
Frontiers in Immunology 2023With the deepening of our understanding of adaptive immunity at the cellular and molecular level, targeting antigens directly to immune cells has proven to be a... (Review)
Review
With the deepening of our understanding of adaptive immunity at the cellular and molecular level, targeting antigens directly to immune cells has proven to be a successful strategy to develop innovative and potent vaccines. Indeed, it offers the potential to increase vaccine potency and/or modulate immune response quality while reducing off-target effects. With mRNA-vaccines establishing themselves as a versatile technology for future applications, in the last years several approaches have been explored to target nanoparticles-enabled mRNA-delivery systems to immune cells, with a focus on dendritic cells. Dendritic cells (DCs) are the most potent antigen presenting cells and key mediators of B- and T-cell immunity, and therefore considered as an ideal target for cell-specific antigen delivery. Indeed, improved potency of DC-targeted vaccines has been proved and . This review discusses the potential specific targets for immune system-directed mRNA delivery, as well as the different targeting ligand classes and delivery systems used for this purpose.
Topics: Dendritic Cells; Vaccines; Adaptive Immunity; T-Lymphocytes; Antigens
PubMed: 38090568
DOI: 10.3389/fimmu.2023.1294929 -
The EMBO Journal Dec 2023Cells secrete extracellular vesicles (EVs) and non-vesicular extracellular (nano)particles (NVEPs or ENPs) that may play a role in intercellular communication....
Cells secrete extracellular vesicles (EVs) and non-vesicular extracellular (nano)particles (NVEPs or ENPs) that may play a role in intercellular communication. Tumor-derived EVs have been proposed to induce immune priming of antigen presenting cells or to be immuno-suppressive agents. We suspect that such disparate functions are due to variable compositions in EV subtypes and ENPs. We aimed to characterize the array of secreted EVs and ENPs of murine tumor cell lines. Unexpectedly, we identified virus-like particles (VLPs) from endogenous murine leukemia virus in preparations of EVs produced by many tumor cells. We established a protocol to separate small EVs from VLPs and ENPs. We compared their protein composition and analyzed their functional interaction with target dendritic cells. ENPs were poorly captured and did not affect dendritic cells. Small EVs specifically induced dendritic cell death. A mixed large/dense EV/VLP preparation was most efficient to induce dendritic cell maturation and antigen presentation. Our results call for systematic re-evaluation of the respective proportions and functions of non-viral EVs and VLPs produced by murine tumors and their contribution to tumor progression.
Topics: Animals; Mice; Endogenous Retroviruses; Extracellular Vesicles; Cell Line, Tumor; Cell Differentiation; Dendritic Cells; Neoplasms
PubMed: 38073509
DOI: 10.15252/embj.2023113590 -
Drug Design, Development and Therapy 2023Malignant melanoma (MM), the most lethal skin cancer, is highly invasive and metastatic. These qualities are related to not only genetic mutations in MM itself but also...
PURPOSE
Malignant melanoma (MM), the most lethal skin cancer, is highly invasive and metastatic. These qualities are related to not only genetic mutations in MM itself but also the interaction of MM cells with the immune system and microenvironment. This study aimed to construct a combined immunotherapy and gene therapy drug delivery system for the effective treatment of MM.
METHODS
Mature dendritic cell (mDC) exosomes (mDexos) with immune induction functions were used as carriers. BRAF siRNA (siBRAF) with the ability to silence mutated BRAF in MM was encapsulated in mDexos by electroporation to construct a biomimetic nanosystem for the codelivery of immunotherapy and gene therapy drugs (siBRAF-mDexos) to the MM microenvironment. Then, we investigated the nanosystem's serum stability and biocompatibility, uptake efficiency in mouse melanoma cells (B16-F10 cells), cytotoxicity against B16-F10 cells and inhibitory effect on BRAF expression. Furthermore, we evaluated its antimelanoma activity and safety in vivo.
RESULTS
SiBRAF-mDexos were nanosized. Compared to siBRAF, siBRAF-mDexos displayed significantly increased serum stability, biocompatibility, uptake efficiency in B16-F10 cells, and cytotoxicity to B16-F10 melanoma cells; they also had a significantly greater inhibitory effect on BRAF expression and induced T-lymphocyte proliferation. Moreover, compared with siBRAF, siBRAF-mDexos showed significantly enhanced anti-MM activity and a high level of safety in vivo.
CONCLUSION
The study suggests that the siBRAF-mDexo biomimetic drug codelivery system can be used to effectively treat MM, which provides a new strategy for combined gene therapy and immunotherapy for MM.
Topics: Animals; Mice; Exosomes; Biomimetics; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Immunotherapy; Drug Delivery Systems; Melanoma, Experimental; Genetic Therapy; Dendritic Cells; Tumor Microenvironment; Melanoma, Cutaneous Malignant
PubMed: 37489176
DOI: 10.2147/DDDT.S414758