scholarly journals Between biology and medicine: perspectives on the use of dendritic cells in anticancer therapy

2017 ◽  
Vol 71 (0) ◽  
pp. 0-0
Author(s):  
Agnieszka Szczygieł ◽  
Elżbieta Pajtasz-Piasecka
Keyword(s):  
Dendritic Cells ◽  
Ex Vivo ◽  
Anticancer Therapy ◽  
Point Of View ◽  
Proper Function ◽  
Innate And Adaptive Immunity ◽  
Factors Affecting ◽  
Antigen Presenting

Dendritic cells (DCs), as a link between innate and adaptive immunity, play a pivotal role in maintaining homeostasis of the immune system. The DC population is characterized by heterogeneity; it consists of many subpopulations which, despite their phenotypic and localization differences, play an essential function – they are professional antigen presenting cells. Due to their role, DCs can be utilized in a new cancer treatment strategy. Their main purpose is to generate an anticancer response leading to the elimination of cancer cells. The tumor microenvironment, abundant in immunosuppressive factors (e.g. IL-10, TGF-β, Arg1, IDO), impairs the proper function of DCs. For this reason, various strategies are necessary for ex vivo preparation of DC-based vaccines and for the support of in vivo DCs to fight against tumors. DC-based vaccines are combined with other forms of immunotherapy (e.g. blockade of immune checkpoint molecules, e.g. PD-1 or CTLA-4) or conventional types of therapies (e.g. chemotherapy). Despite the enormous progress that has been made in anticancer therapy in the past two decades, there are still many unresolved issues regarding the effectiveness of the DCs usage. In this paper we described, in both a mouse and a human subject, a series of DC subpopulations, differentiating in normal conditions or under the influence of cancer microenvironment. We listed factors affecting the quality of the in vivo and ex vivo generations of antitumoral responses, significant from a therapeutic point of view. Moreover, the most important strategies for the use of DCs in anticancer therapies, as well as further developments on this field, have been discussed.

scholarly journals Mast cells acquire MHCII from dendritic cells during skin inflammation

2017 ◽  
Vol 214 (12) ◽  
pp. 3791-3811 ◽  
Author(s):  
Jan Dudeck ◽  
Anna Medyukhina ◽  
Julia Fröbel ◽  
Carl-Magnus Svensson ◽  
Johanna Kotrba ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Mast Cells ◽  
Ex Vivo ◽  
Multiphoton Microscopy ◽  
Skin Inflammation ◽  
Critical Periods ◽  
Reporter Mice ◽  
Antigen Presenting

Mast cells (MCs) and dendritic cells (DCs) are essential innate sentinels populating host-environment interfaces. Using longitudinal intravital multiphoton microscopy of DCGFP/MCRFP reporter mice, we herein provide in vivo evidence that migratory DCs execute targeted cell-to-cell interactions with stationary MCs before leaving the inflamed skin to draining lymph nodes. During initial stages of skin inflammation, DCs dynamically scan MCs, whereas at a later stage, long-lasting interactions predominate. These innate-to-innate synapse-like contacts ultimately culminate in DC-to-MC molecule transfers including major histocompatibility complex class II (MHCII) proteins enabling subsequent ex vivo priming of allogeneic T cells with a specific cytokine signature. The extent of MHCII transfer to MCs correlates with their T cell priming efficiency. Importantly, preventing the cross talk by preceding DC depletion decreases MC antigen presenting capacity and T cell–driven inflammation. Consequently, we identify an innate intercellular communication arming resident MCs with key DC functions that might contribute to the acute defense potential during critical periods of migration-based DC absence.

scholarly journals CYP450-derived oxylipins mediate inflammatory resolution

2016 ◽  
Vol 113 (23) ◽  
pp. E3240-E3249 ◽  
Author(s):  
Derek W. Gilroy ◽  
Matthew L. Edin ◽  
Roel P. H. De Maeyer ◽  
Jonas Bystrom ◽  
Justine Newson ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Adaptive Immunity ◽  
Ex Vivo ◽  
Critical Role ◽  
Regulatory System ◽  
Mononuclear Phagocyte ◽  
Innate And Adaptive Immunity ◽  
Wound Debridement ◽  
Opposing Effects

Resolution of inflammation has emerged as an active process in immunobiology, with cells of the mononuclear phagocyte system being critical in mediating efferocytosis and wound debridement and bridging the gap between innate and adaptive immunity. Here we investigated the roles of cytochrome P450 (CYP)-derived epoxy-oxylipins in a well-characterized model of sterile resolving peritonitis in the mouse. Epoxy-oxylipins were produced in a biphasic manner during the peaks of acute (4 h) and resolution phases (24–48 h) of the response. The epoxygenase inhibitor SKF525A (epoxI) given at 24 h selectively inhibited arachidonic acid- and linoleic acid-derived CYP450-epoxy-oxlipins and resulted in a dramatic influx in monocytes. The epoxI-recruited monocytes were strongly GR1+, Ly6chi, CCR2hi, CCL2hi, and CX3CR1lo. In addition, expression of F4/80 and the recruitment of T cells, B cells, and dendritic cells were suppressed. sEH (Ephx2)−/− mice, which have elevated epoxy-oxylipins, demonstrated opposing effects to epoxI-treated mice: reduced Ly6chi monocytes and elevated F4/80hi macrophages and B, T, and dendritic cells. Ly6chi and Ly6clo monocytes, resident macrophages, and recruited dendritic cells all showed a dramatic change in their resolution signature following in vivo epoxI treatment. Markers of macrophage differentiation CD11b, MerTK, and CD103 were reduced, and monocyte-derived macrophages and resident macrophages ex vivo showed greatly impaired phagocytosis of zymosan and efferocytosis of apoptotic thymocytes following epoxI treatment. These findings demonstrate that epoxy-oxylipins have a critical role in monocyte lineage recruitment and activity to promote inflammatory resolution and represent a previously unidentified internal regulatory system governing the establishment of adaptive immunity.

scholarly journals Tolerogenic Dendritic Cells on Transplantation: Immunotherapy Based on Second Signal Blockage

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Priscila de Matos Silva ◽  
Julia Bier ◽  
Lisiery Negrini Paiatto ◽  
Cassia Galdino Albuquerque ◽  
Caique Lopes Souza ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Immunological Synapse ◽  
Ex Vivo ◽  
Transplant Rejection ◽  
Innate And Adaptive Immunity ◽  
Tolerogenic Dendritic Cells ◽  
Current Therapies ◽  
Antigen Presenting

Dendritic cells (DCs), the most important professional antigen-presenting cells (APC), play crucial role in both immunity and tolerance. It is well known that DCs are able to mount immune responses against foreign antigens and simultaneously tolerate self-antigens. Since DCs can be modulated depending on the surrounding microenvironment, they can act as a bridge between innate and adaptive immunity. However, the mechanisms that support this dual role are not entirely clear. Recent studies have shown that DCs can be manipulatedex vivoin order to trigger their tolerogenic profile, what can be a tool to be used in clinical trials aiming the treatment of various diseases and the prevention of transplant rejection. In this sense, the blockage of costimulatory molecules on DC, in the attempt of inhibiting the second signal in the immunological synapse, can be considered as one of the main strategies under development. This review brings an update on current therapies using tolerogenic dendritic cells modulated with costimulatory blockers with the aim of reducing transplant rejection. However, although there are current clinical trials using tolerogenic DC to treat allograft rejection, the actual challenge is to modulate these cells in order to maintain a permanent tolerogenic profile.

Anti-β2 Glycoprotein I Antibodies Cause Inflammation and Recruit Dendritic Cells in Platelet Clearance

2001 ◽  
Vol 86 (11) ◽  
pp. 1257-1263 ◽  
Author(s):  
Attilio Bondanza ◽  
Angelo Manfredi ◽  
Valérie Zimmermann ◽  
Matteo Iannacone ◽  
Angela Tincani ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Responses ◽  
Glycoprotein I ◽  
Activated Platelets ◽  
Tnf Α ◽  
Per Se ◽  
Antigen Presenting ◽  
Antiinflammatory Cytokine

SummaryScavenger phagocytes are mostly responsible for the in vivo clearance of activated or senescent platelets. In contrast to other particulate substrates, the phagocytosis of platelets does not incite pro-inflammatory responses in vivo. This study assessed the contribution of macrophages and dendritic cells (DCs) to the clearance of activated platelets. Furthermore, we verified whether antibodies against the β2 Glycoprotein I (β2GPI), which bind to activated platelets, influence the phenomenon. DCs did not per se internalise activated platelets. In contrast, macrophages efficiently phagocytosed platelets. In agreement with the uneventful nature of the clearance of platelets in vivo, phagocytosing macrophages did not release IL-1β, TNF-α or IL-10. β2GPI bound to activated platelets and was required for their recognition by anti-ββ2GPI antibodies. DCs internalised platelets opsonised by anti-ββ2GPI antibodies. The phagocytosis of opsonised platelets determined the release of TNF-α and IL-1β by DCs and macrophages. Phagocytosing macrophages, but not DCs, secreted the antiinflammatory cytokine IL-1β0. We conclude that anti-ββ2GPI antibodies cause inflammation during platelet clearance and shuttle platelet antigens to antigen presenting DCs.

scholarly journals Effect of ethanol and cocaine on [11C]MPC-6827 uptake in SH-SY5Y cells

2021 ◽  
Author(s):  
Naresh Damuka ◽  
Miranda Orr ◽  
Paul W. Czoty ◽  
Jeffrey L. Weiner ◽  
Thomas J. Martin ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Ex Vivo ◽  
Neuroblastoma Cells ◽  
Proper Function ◽  
Brain Functions ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Vitro Binding

AbstractMicrotubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Alcohol and substance use disorders (AUD/SUDs) affects the function and organization of MTs in the brain, making them a potential neuroimaging marker to study the resulting impairment of overall neurobehavioral and cognitive processes. Our lab reported the first brain-penetrant MT-tracking Positron Emission Tomography (PET) ligand [11C]MPC-6827 and demonstrated its in vivo utility in rodents and non-human primates. To further explore the in vivo imaging potential of [11C]MPC-6827, we need to investigate its mechanism of action. Here, we report preliminary in vitro binding results in SH-SY5Y neuroblastoma cells exposed to ethanol (EtOH) or cocaine in combination with multiple agents that alter MT stability. EtOH and cocaine treatments increased MT stability and decreased free tubulin monomers. Our initial cell-binding assay demonstrated that [11C]MPC-6827 may have high affinity to free/unbound tubulin units. Consistent with this mechanism of action, we observed lower [11C]MPC-6827 uptake in SH-SY5Y cells after EtOH and cocaine treatments (e.g., fewer free tubulin units). We are currently performing in vivo PET imaging and ex vivo biodistribution studies in rodent and nonhuman primate models of AUD and SUDs and Alzheimer's disease.

A novel mouse model based on intersectional genetics enables unambiguous in vivo discrimination between plasmacytoid and other dendritic cells and their comparative characterization

2022 ◽  
Author(s):  
Michael Valente ◽  
Nils Collinet ◽  
Thien-Phong Vu Manh ◽  
Karima Naciri ◽  
Gilles Bessou ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Steady State ◽  
Mouse Model ◽  
Single Cell ◽  
Ex Vivo ◽  
High Specificity ◽  
Type I ◽  
Specific Expression ◽  
Physiological Functions

Plasmacytoid dendritic cells (pDC) were identified about 20 years ago, based on their unique ability to rapidly produce copious amounts of all subsets of type I and type III interferon (IFN-I/III) upon virus sensing, while being refractory to infection. Yet, the identity and physiological functions of pDC are still a matter of debate, in a large part due to their lack of specific expression of any single cell surface marker or gene that would allow to track them in tissues and to target them in vivo with high specificity and penetrance. Indeed, recent studies showed that previous methods that were used to identify or deplete pDC also targeted other cell types, including pDC-like cells and transitional DC (tDC) that were proposed to be responsible for all the antigen presentation ability previously attributed to steady state pDC. Hence, improving our understanding of the nature and in vivo choreography of pDC physiological functions requires the development of novel tools to unambiguously identify and track these cells, including in comparison to pDC-like cells and tDC. Here, we report successful generation of a pDC-reporter mouse model, by using an intersectional genetic strategy based on the unique co-expression of Siglech and Pacsin1 in pDC. This pDC-Tomato mouse strain allows specific ex vivo and in situ detection of pDC. Breeding them with Zbtb46GFP mice allowed side-by-side purification and transcriptional profiling by single cell RNA sequencing of bona fide pDC, pDC-like cells and tDC, in comparison to type 1 and 2 conventional DC (cDC1 and cDC2), both at steady state and during a viral infection, revealing diverging activation patterns of pDC-like cells and tDC. Finally, by breeding pDC-Tomato mice with Ifnb1EYFP mice, we determined the choreography of pDC recruitment to the micro-anatomical sites of viral replication in the spleen, with initially similar but later divergent behaviors of the pDC that engaged or not into IFN-I production. Our novel pDC-Tomato mouse model, and newly identified gene modules specific to combinations of DC types and activations states, will constitute valuable resources for a deeper understanding of the functional division of labor between DC types and its molecular regulation at homeostasis and during viral infections.

Antithymocyte Globulin Induces Ex Vivo and In Vivo Depletion of Myeloid and Plasmacytoid Dendritic Cells

2005 ◽  
Vol 79 (3) ◽  
pp. 369-371 ◽  
Author(s):  
Lubin Fang ◽  
Boris Fehse ◽  
Melanie Engel ◽  
Axel Zander ◽  
Nicolaus Kr??ger
Keyword(s):  
Dendritic Cells ◽  
Antithymocyte Globulin ◽  
Ex Vivo ◽  
Plasmacytoid Dendritic Cells

scholarly journals In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis

2006 ◽  
Vol 74 (7) ◽  
pp. 3817-3824 ◽  
Author(s):  
Karen L. Wozniak ◽  
Jatin M. Vyas ◽  
Stuart M. Levitz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Mouse Lung

ABSTRACT Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.

scholarly journals CD1: From Molecules to Diseases

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1909 ◽  
Author(s):  
D. Branch Moody ◽  
Sara Suliman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Cell Receptor ◽  
High Genetic Diversity ◽  
Disease States ◽  
New Research ◽  
Antigen Presenting ◽  
Cluster Of Differentiation

The human cluster of differentiation (CD)1 system for antigen display is comprised of four types of antigen-presenting molecules, each with a distinct functional niche: CD1a, CD1b, CD1c, and CD1d. Whereas CD1 proteins were thought solely to influence T-cell responses through display of amphipathic lipids, recent studies emphasize the role of direct contacts between the T-cell receptor and CD1 itself. Moving from molecules to diseases, new research approaches emphasize human CD1-transgenic mouse models and the study of human polyclonal T cells in vivo or ex vivo in disease states. Whereas the high genetic diversity of major histocompatibility complex (MHC)-encoded antigen-presenting molecules provides a major hurdle for designing antigens that activate T cells in all humans, the simple population genetics of the CD1 system offers the prospect of discovering or designing broadly acting immunomodulatory agents.

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