scholarly journals The roles of tumor-derived exosomes in altered differentiation, maturation and function of dendritic cells

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Reza Hosseini ◽  
Leila Asef-Kabiri ◽  
Hassan Yousefi ◽  
Hamzeh Sarvnaz ◽  
Majid Salehi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Treatment Options ◽  
Vaccination Strategy ◽  
Therapeutic Approaches ◽  
Therapeutic Level ◽  
Tumor Exosomes ◽  
And Function ◽  
Insight Into ◽  
Dominant Influence

AbstractTumor-derived exosomes (TDEs) have been shown to impede anti-tumor immune responses via their immunosuppressive cargo. Since dendritic cells (DCs) are the key mediators of priming and maintenance of T cell-mediated responses; thus it is logical that the exosomes released by tumor cells can exert a dominant influence on DCs biology. This paper intends to provide a mechanistic insight into the TDEs-mediated DCs abnormalities in the tumor context. More importantly, we discuss extensively how tumor exosomes induce subversion of DCs differentiation, maturation and function in separate sections. We also briefly describe the importance of TDEs at therapeutic level to help guide future treatment options, in particular DC-based vaccination strategy, and review advances in the design and discovery of exosome inhibitors. Understanding the exosomal content and the pathways by which TDEs are responsible for immune evasion may help to revise treatment rationales and devise novel therapeutic approaches to overcome the hurdles in cancer treatment.

scholarly journals Congenital Deficiency of Conventional Dendritic Cells Promotes the Development of Atopic Dermatitis-Like Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yotaro Nishikawa ◽  
Tomohiro Fukaya ◽  
Takehito Fukui ◽  
Tomofumi Uto ◽  
Hideaki Takagi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Atopic Dermatitis ◽  
Immune Responses ◽  
Skin Barrier ◽  
Lymphoid Cells ◽  
Congenital Deficiency ◽  
T Cell Immune Responses ◽  
Group 2 ◽  
And Function ◽  
The Impact

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease characterized by impaired epidermal barrier function and dysregulation of Thelper-2 (TH2)-biased immune responses. While the lineage of conventional dendritic cells (cDCs) are implicated to play decisive roles in T-cell immune responses, their requirement for the development of AD remains elusive. Here, we describe the impact of the constitutive loss of cDCs on the progression of AD-like inflammation by using binary transgenic (Tg) mice that constitutively lacked CD11chi cDCs. Unexpectedly, the congenital deficiency of cDCs not only exacerbates the pathogenesis of AD-like inflammation but also elicits immune abnormalities with the increased composition and function of granulocytes and group 2 innate lymphoid cells (ILC2) as well as B cells possibly mediated through the breakdown of the Fms-related tyrosine kinase 3 ligand (Flt3L)-mediated homeostatic feedback loop. Furthermore, the constitutive loss of cDCs accelerates skin colonization of Staphylococcus aureus (S. aureus), that associated with disease flare. Thus, cDCs maintains immune homeostasis to prevent the occurrence of immune abnormalities to maintain the functional skin barrier for mitigating AD flare.

CXCR4 signaling controls dendritic cell location and activation at steady-state and in inflammation

Blood ◽  
2021 ◽  
Author(s):  
Carmen Gallego ◽  
Mathias Vétillard ◽  
Joseph Calmette ◽  
Mélanie Roriz ◽  
Viviana Marin-Esteban ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Steady State ◽  
Immune Responses ◽  
Chemokine Receptors ◽  
High Susceptibility ◽  
Cxcr4 Signaling ◽  
Whim Syndrome ◽  
Plasmacytoid Dcs ◽  
And Function ◽  
Specific Contribution

Dendritic cells (DCs) encompass several cell subsets that collaborate to initiate and regulate immune responses. Proper DC localization determines their function and requires the tightly controlled action of chemokine receptors. All DC subsets express CXCR4, but the genuine contribution of this receptor to their biology has been overlooked. We addressed this question using natural CXCR4 mutants resistant to CXCL12-induced desensitization and harboring a gain of function that cause the warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) Syndrome (WS), a rare immunodeficiency associated with high susceptibility to the pathogenesis of human papillomavirus (HPV). We report a reduction in the number of circulating plasmacytoid DCs (pDCs) in WHIM patients, whereas that of conventional DCs is preserved. This pattern was reproduced in an original mouse model of WS, enabling us to show that the circulating pDC defect can be corrected upon CXCR4 blockade and that pDC differentiation and function are preserved, despite CXCR4 dysfunction. We further identified proper CXCR4 signaling as a critical checkpoint for Langerhans-cell and DC migration from the skin to lymph nodes, with corollary alterations of their activation state and tissue inflammation in a model of HPV-induced dysplasia. Beyond providing new hypotheses to explain the susceptibility of WHIM patients to HPV pathogenesis, this study shows that proper CXCR4 signaling establishes a migration threshold that controls DC egress from CXCL12-containing environments and highlights the critical and subset-specific contribution of CXCR4 signal termination to DC biology.

scholarly journals Rousette Bat Dendritic Cells Overcome Marburg Virus-Mediated Antiviral Responses by Upregulation of Interferon-Related Genes While Downregulating Proinflammatory Disease Mediators

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Joseph Prescott ◽  
Jonathan C. Guito ◽  
Jessica R. Spengler ◽  
Catherine E. Arnold ◽  
Amy J. Schuh ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Human Disease ◽  
Inflammatory Responses ◽  
Virus Disease ◽  
Marburg Virus ◽  
Transcriptional Responses ◽  
Adaptive Immune ◽  
Insight Into

ABSTRACT Dysregulated and maladaptive immune responses are at the forefront of human diseases caused by infection with zoonotic viral hemorrhagic fever viruses. Elucidating mechanisms of how the natural animal reservoirs of these viruses coexist with these agents without overt disease, while permitting sufficient replication to allow for transmission and maintenance in a population, is important for understanding the viral ecology and spillover to humans. The Egyptian rousette bat (ERB) has been identified as a reservoir for Marburg virus (MARV), a filovirus and the etiological agent of the highly lethal Marburg virus disease. Little is known regarding how these bats immunologically respond to MARV infection. In humans, macrophages and dendritic cells (DCs) are primary targets of infection, and their dysregulation is thought to play a central role in filovirus diseases, by disturbing their normal functions as innate sensors and adaptive immune response facilitators while serving as amplification and dissemination agents for the virus. The infection status and responses to MARV in bat myeloid-lineage cells are uncharacterized and likely represent an important modulator of the bat’s immune response to MARV infection. Here, we generate DCs from the bone marrow of rousette bats. Infection with a bat isolate of MARV resulted in a low level of transcription in these cells and significantly downregulated DC maturation and adaptive immune-stimulatory pathways while simultaneously upregulating interferon-related pathogen-sensing pathways. This study provides a first insight into how the bat immune response is directed toward preventing aberrant inflammatory responses while mounting an antiviral response to defend against MARV infection. IMPORTANCE Marburg viruses (MARVs) cause severe human disease resulting from aberrant immune responses. Dendritic cells (DCs) are primary targets of infection and are dysregulated by MARV. Dysregulation of DCs facilitates MARV replication and virus dissemination and influences downstream immune responses that result in immunopathology. Egyptian rousette bats (ERBs) are natural reservoirs of MARV, and infection results in virus replication and shedding, with asymptomatic control of the virus within weeks. The mechanisms that bats employ to appropriately respond to infection while avoiding disease are unknown. Because DC infection and modulation are important early events in human disease, we measured the transcriptional responses of ERB DCs to MARV. The significance of this work is in identifying cell type-specific coevolved responses between ERBs and MARV, which gives insight into how bat reservoirs are able to harbor MARV and permit viral replication, allowing transmission and maintenance in the population while simultaneously preventing immunopathogenesis.

scholarly journals Mechanobiological Principles Influence the Immune Response in Regeneration: Implications for Bone Healing

2021 ◽  
Vol 9 ◽  
Author(s):  
Raphael S. Knecht ◽  
Christian H. Bucher ◽  
Sophie Van Linthout ◽  
Carsten Tschöpe ◽  
Katharina Schmidt-Bleek ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Matrix ◽  
Immune Responses ◽  
Tissue Regeneration ◽  
Immune Cells ◽  
Material Properties ◽  
Treatment Options ◽  
Hematopoietic Cells ◽  
Therapeutic Approaches ◽  
New Treatment

A misdirected or imbalanced local immune composition is often one of the reasons for unsuccessful regeneration resulting in scarring or fibrosis. Successful healing requires a balanced initiation and a timely down-regulation of the inflammation for the re-establishment of a biologically and mechanically homeostasis. While biomaterial-based approaches to control local immune responses are emerging as potential new treatment options, the extent to which biophysical material properties themselves play a role in modulating a local immune niche response has so far been considered only occasionally. The communication loop between extracellular matrix, non-hematopoietic cells, and immune cells seems to be specifically sensitive to mechanical cues and appears to play a role in the initiation and promotion of a local inflammatory setting. In this review, we focus on the crosstalk between ECM and its mechanical triggers and how they impact immune cells and non-hematopoietic cells and their crosstalk during tissue regeneration. We realized that especially mechanosensitive receptors such as TRPV4 and PIEZO1 and the mechanosensitive transcription factor YAP/TAZ are essential to regeneration in various organ settings. This indicates novel opportunities for therapeutic approaches to improve tissue regeneration, based on the immune-mechanical principles found in bone but also lung, heart, and skin.

scholarly journals Apoptosis and dysfunction of blood dendritic cells in patients with falciparum and vivax malaria

2013 ◽  
Vol 210 (8) ◽  
pp. 1635-1646 ◽  
Author(s):  
Alberto Pinzon-Charry ◽  
Tonia Woodberry ◽  
Vivian Kienzle ◽  
Virginia McPhun ◽  
Gabriela Minigo ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Acute Infection ◽  
Plasmodium Infection ◽  
Spontaneous Apoptosis ◽  
Cross Sectional ◽  
And Function ◽  
Immature Cells

Malaria causes significant morbidity worldwide and a vaccine is urgently required. Plasmodium infection causes considerable immune dysregulation, and elicitation of vaccine immunity remains challenging. Given the central role of dendritic cells (DCs) in initiating immunity, understanding their biology during malaria will improve vaccination outcomes. Circulating DCs are particularly important, as they shape immune responses in vivo and reflect the functional status of other subpopulations. We performed cross-sectional and longitudinal assessments of the frequency, phenotype, and function of circulating DC in 67 Papuan adults during acute uncomplicated P. falciparum, P. vivax, and convalescent P. falciparum infections. We demonstrate that malaria patients display a significant reduction in circulating DC numbers and the concurrent accumulation of immature cells. Such alteration is associated with marked levels of spontaneous apoptosis and impairment in the ability of DC to mature, capture, and present antigens to T cells. Interestingly, sustained levels of plasma IL-10 were observed in patients with acute infection and were implicated in the induction of DC apoptosis. DC apoptosis was reversed upon IL-10 blockade, and DC function recovered when IL-10 levels returned to baseline by convalescence. Our data provide key information on the mechanisms behind DC suppression during malaria and will assist in developing strategies to better harness DC’s immunotherapeutic potential.

RNA-loaded dendritic cells: more than a tour de force in cancer therapeutics

Immunotherapy ◽  
2019 ◽  
Vol 11 (13) ◽  
pp. 1129-1147
Author(s):  
Aishwarya Joshi ◽  
Nikunj Tandel ◽  
Priyanka Tyagi ◽  
Sarat K Dalai ◽  
Prakash S Bisen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Conventional Treatment ◽  
Treatment Options ◽  
Cancer Therapeutics ◽  
Therapeutic Strategies ◽  
Vital Role ◽  
Delivery Vehicles ◽  
Immune Competency ◽  
Potential Use

A wide array of therapeutic strategies has been implemented against cancers, yet their clinical benefit is limited. The lack of clinical efficacy of the conventional treatment options might be due to the inept immune competency of the patients. Dendritic cells (DCs) have a vital role in initiating and directing immune responses and have been frequently used as delivery vehicles in clinical research. The recent clinical data suggest the potential use of DCs pulsed with nucleic acid, especially with RNA holds a great potential as an immunotherapeutic measure with compare to other cancer therapeutics. This review mainly deals with the DCs and their role in transfection with RNA in cancer immunotherapy.

scholarly journals Understanding the development of amblyopia using macaque monkey models

2019 ◽  
Vol 116 (52) ◽  
pp. 26217-26223 ◽  
Author(s):  
Lynne Kiorpes
Keyword(s):  
Macaque Monkey ◽  
Therapeutic Approaches ◽  
Ongoing Research ◽  
History Of ◽  
Visual Motor ◽  
Perceptual Abilities ◽  
High Level ◽  
And Function ◽  
The Brain ◽  
Insight Into

Amblyopia is a sensory developmental disorder affecting as many as 4% of children around the world. While clinically identified as a reduction in visual acuity and disrupted binocular function, amblyopia affects many low- and high-level perceptual abilities. Research with nonhuman primate models has provided much needed insight into the natural history of amblyopia, its origins and sensitive periods, and the brain mechanisms that underly this disorder. Amblyopia results from abnormal binocular visual experience and impacts the structure and function of the visual pathways beginning at the level of the primary visual cortex (V1). However, there are multiple instances of abnormalities in areas beyond V1 that are not simply inherited from earlier stages of processing. The full constellation of deficits must be taken into consideration in order to understand the broad impact of amblyopia on visual and visual–motor function. The data generated from studies of animal models of the most common forms of amblyopia have provided indispensable insight into the disorder, which has significantly impacted clinical practice. It is expected that this translational impact will continue as ongoing research into the neural correlates of amblyopia provides guidance for novel therapeutic approaches.

Dendritic Cells as Arbiters of Peritoneal Immune Responses

2006 ◽  
Vol 26 (1) ◽  
pp. 8-25 ◽  
Author(s):  
Michelle L. McCully ◽  
Joaquín Madrenas
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Immune Defense ◽  
Dendritic Cell Differentiation ◽  
Adaptive Immune ◽  
The Past ◽  
Key Players ◽  
And Function

During the past few years, there has been a substantial increase in the understanding of innate immunity. Dendritic cells are emerging as key players in the orchestration of this early phase of immune responses, with a role that will translate into the subsequent type of adaptive immune response against infection. Here we provide an overview of dendritic cell differentiation and function, with particular emphasis on those features unique to the immune defense of the peritoneal cavity and in the context of peritoneal dialysis-associated immune responses. The reader is referred to the primary references included in the accompanying list for specific details in this fascinating field.

Curcumin: a dietary phytochemical for targeting the phenotype and function of dendritic cells

2020 ◽  
Vol 27 ◽  
Author(s):  
Kaveh Rahimi ◽  
Kambiz Hassanzadeh ◽  
Hashem Khanbabaei ◽  
Saeed Mohammadian Haftcheshmeh ◽  
Abbas Ahmadi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Intracellular Signaling ◽  
T Helper 1 ◽  
Cytokines And Chemokines ◽  
Wide Range ◽  
Health And Disease ◽  
And Function ◽  
Antigen Presenting ◽  
Tolerogenic Dcs

: Dendritic cells (DCs) are the most powerful antigen-presenting cells which link the innate and adaptive immune responses. Depending on the context DCs initiate the immune responses or contribute to immune tolerance. Any disturbance in their phenotypes and functions may initiate inflammatory or autoimmune diseases. Hence, dysregulated DCs are the most attractive pharmacological target for the development of new therapies aiming at reducing their immunogenicity and at enhancing their tolerogenicity. Curcumin is the polyphenolic phytochemical component of the spice turmeric with a wide range of pharmacological activities. It acts in several ways as a modulator of DCs and converts them into tolerogenic DCs. Tolerogenic DCs possess anti-inflammatory and immunomodulatory activities that regulate the immune responses in health and disease. Curcumin by blocking maturation markers, cytokines and chemokines expression, and disrupting the antigen-presenting machinery of DCs render them non- or hypo-responsive to immunostimulants. It also reduces the expression of co-stimulatory and adhesion molecules on DCs and prevents them from both migration and antigen presentation but enhances their endocytosis capacity. Hence, curcumin causes DCs-inducing regulatory T cells and dampens CD4+ T helper 1 (Th1), Th2, and Th17 polarization. Inhibition of transcription factors such as NF-κB, AP-1, MAPKs (p38, JNK, ERK) and other intracellular signaling molecules such as JAK/STAT/SOCS provide a plausible explanation for most of these observations. In this review, we summarize the potential effects of curcumin on the phenotypes and functions of DCs as the key players in orchestration, stimulation, and modulation of the immune responses.

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