scholarly journals Recent Advances in Good Manufacturing Practice-Grade Generation of Dendritic Cells

2020 ◽  
Vol 47 (6) ◽  
pp. 454-463
Author(s):  
Sarah Cunningham ◽  
Holger Hackstein
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Good Manufacturing Practice ◽  
Clinical Applications ◽  
Small Scale ◽  
Adaptive Immune ◽  
Recent Advances ◽  
Experimental Approaches ◽  
Key Features

Dendritic cells (DCs) are pivotal regulators of immune responses, specialized in antigen presentation and bridging the gap between the innate and adaptive immune system. Due to these key features, DCs have become a pillar of the continuously growing field of cellular therapies. Here we review recent advances in good manufacturing practice strategies and their individual specificities in relation to DC production for clinical applications. These take into account both small-scale experimental approaches as well as automated systems for patient care.

scholarly journals Lactate-Dependent Regulation of Immune Responses by Dendritic Cells and Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Indumathi Manoharan ◽  
Puttur D. Prasad ◽  
Muthusamy Thangaraju ◽  
Santhakumar Manicassamy
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Adaptive Immune Responses ◽  
Effector Functions ◽  
Tissue Microenvironment ◽  
Adaptive Immune ◽  
Pathological Conditions ◽  
Recent Advances ◽  
Adaptive Immune Cells

For decades, lactate has been considered an innocuous bystander metabolite of cellular metabolism. However, emerging studies show that lactate acts as a complex immunomodulatory molecule that controls innate and adaptive immune cells’ effector functions. Thus, recent advances point to lactate as an essential and novel signaling molecule that shapes innate and adaptive immune responses in the intestine and systemic sites. Here, we review these recent advances in the context of the pleiotropic effects of lactate in regulating diverse functions of immune cells in the tissue microenvironment and under pathological conditions.

scholarly journals Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2–MyD88 signal pathway in dendritic cells and enhances Th2 immune responses

2008 ◽  
Vol 205 (1) ◽  
pp. 79-90 ◽  
Author(s):  
De Yang ◽  
Qian Chen ◽  
Shao Bo Su ◽  
Ping Zhang ◽  
Kahori Kurosaka ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Secretory Protein ◽  
Myeloid Differentiation ◽  
Toll Like Receptor ◽  
T Helper ◽  
Adaptive Immune ◽  
Eosinophil Granule ◽  
Myeloid Differentiation Factor

Eosinophil-derived neurotoxin (EDN) is an eosinophil granule–derived secretory protein with ribonuclease and antiviral activity. We have previously shown that EDN can induce the migration and maturation of dendritic cells (DCs). Here, we report that EDN can activate myeloid DCs by triggering the Toll-like receptor (TLR)2–myeloid differentiation factor 88 signaling pathway, thus establishing EDN as an endogenous ligand of TLR2. EDN activates TLR2 independently of TLR1 or TLR6. When mice were immunized with ovalbumin (OVA) together with EDN or with EDN-treated OVA-loaded DCs, EDN enhanced OVA-specific T helper (Th)2-biased immune responses as indicated by predominant production of OVA-specific interleukin (IL)-5, IL-6, IL-10, and IL-13, as well as higher levels of immunoglobulin (Ig)G1 than IgG2a. Based on its ability to serve as a chemoattractant and activator of DCs, as well as the capacity to enhance antigen-specific immune responses, we consider EDN to have the properties of an endogenous alarmin that alerts the adaptive immune system for preferential enhancement of antigen-specific Th2 immune responses.

Dendritic cells in atherosclerosis: Functions in immune regulation and beyond

2011 ◽  
Vol 106 (11) ◽  
pp. 772-778 ◽  
Author(s):  
Helga Manthey ◽  
Alma Zernecke
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Cholesterol Homeostasis ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Vaccination Strategies ◽  
Atherosclerotic Lesions ◽  
Experimental Approaches ◽  
Lesion Growth ◽  
Progression Of Atherosclerosis

SummaryChronic inflammation drives the development of atherosclerosis. Dendritic cells (DCs) are known as central mediators of adaptive immune responses and the development of immunological memory and tolerance. DCs are present in non-diseased arteries, and accumulate within atherosclerotic lesions where they can be localised in close vicinity to T cells. Recent work has revealed important functions of DCs in regulating immune mechanisms in atherogenesis, and vaccination strategies using DCs have been explored for treatment of disease. However, in line with a phenotypical and functional overlap with plaque macrophages vascular DCs were also identified to engulf lipids, thus contributing to lipid burden in the vessel wall and initiation of lesion growth. Furthermore, a function of DCs in regulating cholesterol homeostasis has been revealed. Finally, phenotypically distinct plasmacytoid dendritic cells (pDCs) have been identified within atherosclerotic lesions. This review will dissect the multifaceted contribution of DCs and pDCs to the initiation and progression of atherosclerosis and the experimental approaches utilising DCs in therapeutic vaccination strategies.

scholarly journals Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mauro Di Pilato ◽  
Miguel Palomino-Segura ◽  
Ernesto Mejías-Pérez ◽  
Carmen E. Gómez ◽  
Andrea Rubio-Ponce ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Adaptive Immune System ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Adaptive Immune

AbstractNeutrophils are innate immune cells involved in the elimination of pathogens and can also induce adaptive immune responses. Nα and Nβ neutrophils have been described with distinct in vitro capacity to generate antigen-specific CD8 T-cell responses. However, how these cell types exert their role in vivo and how manipulation of Nβ/Nα ratio influences vaccine-mediated immune responses are not known. In this study, we find that these neutrophil subtypes show distinct migratory and motility patterns and different ability to interact with CD8 T cells in the spleen following vaccinia virus (VACV) infection. Moreover, after analysis of adhesion, inflammatory, and migration markers, we observe that Nβ neutrophils overexpress the α4β1 integrin compared to Nα. Finally, by inhibiting α4β1 integrin, we increase the Nβ/Nα ratio and enhance CD8 T-cell responses to HIV VACV-delivered antigens. These findings provide significant advancements in the comprehension of neutrophil-based control of adaptive immune system and their relevance in vaccine design.

scholarly journals Rapamycin Alternatively Modifies Mitochondrial Dynamics in Dendritic Cells to Reduce Kidney Ischemic Reperfusion Injury

2021 ◽  
Vol 22 (10) ◽  
pp. 5386
Author(s):  
Maria Namwanje ◽  
Bijay Bisunke ◽  
Thomas V. Rousselle ◽  
Gene G. Lamanilao ◽  
Venkatadri S. Sunder ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Mitochondrial Dynamics ◽  
Graft Loss ◽  
Kidney Injury ◽  
Adaptive Immune ◽  
Consumption Rates ◽  
Regulatory Phenotype

Dendritic cells (DCs) are unique immune cells that can link innate and adaptive immune responses and Immunometabolism greatly impacts their phenotype. Rapamycin is a macrolide compound that has immunosuppressant functions and is used to prevent graft loss in kidney transplantation. The current study evaluated the therapeutic potential of ex-vivo rapamycin treated DCs to protect kidneys in a mouse model of acute kidney injury (AKI). For the rapamycin single (S) treatment (Rapa-S-DC), Veh-DCs were treated with rapamycin (10 ng/mL) for 1 h before LPS. In contrast, rapamycin multiple (M) treatment (Rapa-M-DC) were exposed to 3 treatments over 7 days. Only multiple ex-vivo rapamycin treatments of DCs induced a persistent reprogramming of mitochondrial metabolism. These DCs had 18-fold more mitochondria, had almost 4-fold higher oxygen consumption rates, and produced more ATP compared to Veh-DCs (Veh treated control DCs). Pathway analysis showed IL10 signaling as a major contributing pathway to the altered immunophenotype after Rapamycin treatment compared to vehicle with significantly lower cytokines Tnfa, Il1b, and Il6, while regulators of mitochondrial content Pgc1a, Tfam, and Ho1 remained elevated. Critically, adoptive transfer of rapamycin-treated DCs to WT recipients 24 h before bilateral kidney ischemia significantly protected the kidneys from injury with a significant 3-fold improvement in kidney function. Last, the infusion of DCs containing higher mitochondria numbers (treated ex-vivo with healthy isolated mitochondria (10 µg/mL) one day before) also partially protected the kidneys from IRI. These studies demonstrate that pre-emptive infusion of ex-vivo reprogrammed DCs that have higher mitochondria content has therapeutic capacity to induce an anti-inflammatory regulatory phenotype to protect kidneys from injury.

scholarly journals CD8+lineage dendritic cells determine adaptive immune responses to inflammasome activation upon sterile skin injury

2017 ◽  
Vol 27 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Rituparna Chakraborty ◽  
Janin Chandra ◽  
Shuai Cui ◽  
Lynn Tolley ◽  
Matthew A. Cooper ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Inflammasome Activation ◽  
Adaptive Immune Responses ◽  
Skin Injury ◽  
Adaptive Immune

scholarly journals Dendritic Cells in Innate and Adaptive Immune Responses against Influenza Virus

Viruses ◽  
2009 ◽  
Vol 1 (3) ◽  
pp. 1022-1034 ◽  
Author(s):  
Artur Summerfield ◽  
Kenneth McCullough
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

scholarly journals IN LABORATORY GENERATION AND MATURATION OF HUMAN MONOCYTE-DERIVED DENDRITIC CELLS FOR CANCER IMMUNOTHERAPY

2020 ◽  
pp. 46-52
Author(s):  
KANCHAN K. MISHRA ◽  
SUMIT BHARADVA ◽  
MEGHNAD G. JOSHI ◽  
ARVIND GULBAKE
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Gradient Centrifugation ◽  
Critical Role ◽  
Human Monocyte ◽  
Blood Monocytes ◽  
Adaptive Immune ◽  
Immunodeficiency Virus ◽  
Adaptive Immune Systems

Dendritic cells (DCs) play a critical role in the regulation of adaptive immune responses, furthermore they act as a bridge between the innate and the adaptive immune systems they have been ideal candidates for cell-based immunotherapy of cancers and infections in humans. The first reported trial using DCs in 1995, since they have been used in trials all over the world for several of indications, including cancer and human immunodeficiency virus infection. Generally, for in vitro experiments or for DCs vaccination monocyte-derived dendritic cells (moDCs) were generated from purified monocytes that isolated from peripheral blood by density gradient centrifugation. A variety of methods can be used for enrichment of monocytes for generation of clinical-grade DCs. Herein we summarized up to date understanding of systems and inputs used in procedures to differentiate DCs from blood monocytes in vitro.

scholarly journals The neuropeptide receptor NMUR-1 regulates the specificity of C. elegans innate immunity against pathogen infection

2021 ◽  
Author(s):  
Phillip Wibisono ◽  
Shawndra Wibisono ◽  
Jan Watteyne ◽  
Chia-Hui Chen ◽  
Durai Sellegounder ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Genes ◽  
C Elegans ◽  
Adaptive Immune ◽  
Functional Assays

A key question in current immunology is how the innate immune system generates high levels of specificity. Like most invertebrates, Caenorhabditis elegans does not have an adaptive immune system and relies solely on innate immunity to defend itself against pathogen attacks, yet it can still differentiate different pathogens and launch distinct innate immune responses. Here, we have found that functional loss of NMUR-1, a neuronal GPCR homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans survival against various bacterial pathogens. Transcriptomic analyses and functional assays revealed that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens. Our study has uncovered a molecular basis for the specificity of C. elegans innate immunity that could provide mechanistic insights into understanding the specificity of vertebrate innate immunity.

Impact of gut microbiota on immune system

2021 ◽  
Author(s):  
Farhad Riazi-Rad ◽  
Ava Behrouzi ◽  
Hoora Mazaheri ◽  
Asal Katebi ◽  
Soheila Ajdary
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Disease Susceptibility ◽  
Adaptive Immune System ◽  
Vital Role ◽  
Symbiotic Relationship ◽  
Adaptive Immune ◽  
Physiological Homeostasis ◽  
Environmental Antigens

AbstractThe commensal microflora collection known as microbiota has an essential role in maintaining the host's physiological homeostasis. The microbiota has a vital role in induction and regulation of local and systemic immune responses. On the other hand, the immune system involves maintaining microbiota compositions. Optimal microbiota-immune system cross-talk is essential for protective responses to pathogens and immune tolerance to self and harmless environmental antigens. Any change in this symbiotic relationship may cause susceptibility to diseases. The association of various cancers and auto-immune diseases with microbiota has been proven. Here we review the interaction of immune responses to gut microbiota, focusing on innate and adaptive immune system and disease susceptibility.

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