scholarly journals Immunobiology of Atherosclerosis: A Complex Net of Interactions

2019 ◽  
Vol 20 (21) ◽  
pp. 5293 ◽  
Author(s):  
Herrero-Fernandez ◽  
Gomez-Bris ◽  
Somovilla-Crespo ◽  
Gonzalez-Granado
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Atherosclerotic Lesion ◽  
Chronic Inflammatory Disease ◽  
Principal Factor ◽  
Global Perspective ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune ◽  
Apoptosis And Necrosis

Cardiovascular disease is the leading cause of mortality worldwide, and atherosclerosis the principal factor underlying cardiovascular events. Atherosclerosis is a chronic inflammatory disease characterized by endothelial dysfunction, intimal lipid deposition, smooth muscle cell proliferation, cell apoptosis and necrosis, and local and systemic inflammation, involving key contributions to from innate and adaptive immunity. The balance between proatherogenic inflammatory and atheroprotective anti-inflammatory responses is modulated by a complex network of interactions among vascular components and immune cells, including monocytes, macrophages, dendritic cells, and T, B, and foam cells; these interactions modulate the further progression and stability of the atherosclerotic lesion. In this review, we take a global perspective on existing knowledge about the pathogenesis of immune responses in the atherosclerotic microenvironment and the interplay between the major innate and adaptive immune factors in atherosclerosis. Studies such as this are the basis for the development of new therapies against atherosclerosis

scholarly journals Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Qin Zhao ◽  
Miusi Shi ◽  
Chengcheng Yin ◽  
Zifan Zhao ◽  
Jinglun Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
T Cell Response ◽  
Dual Wavelength ◽  
M2 Macrophage ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

AbstractThe immune response of a biomaterial determines its osteoinductive effect. Although the mechanisms by which some immune cells promote regeneration have been revealed, the biomaterial-induced immune response is a dynamic process involving multiple cells. Currently, it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials. Herein, we investigated the roles of macrophages and dendritic cells (DCs) during the osteoinduction of biphasic calcium phosphate (BCP) scaffolds. We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation, resulting in low T cell response and efficient osteogenesis. Accordingly, a dual-targeting nano-in-micro scaffold (BCP loaded with gold nanocage, BCP-GNC) was designed to regulate the immune responses of macrophages and DCs. Through a dual-wavelength photosensitive switch, BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs, creating a desirable inflammatory environment for osteogenesis. This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.

scholarly journals The fate of influenza A virus after infection of human macrophages and dendritic cells

2012 ◽  
Vol 93 (11) ◽  
pp. 2315-2325 ◽  
Author(s):  
Kirsty R. Short ◽  
Andrew G. Brooks ◽  
Patrick C. Reading ◽  
Sarah L. Londrigan
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Immune Cells ◽  
Influenza A ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Virus Release ◽  
Adaptive Immune ◽  
Human Immune

Airway macrophages (MΦ) and dendritic cells (DC) are important components of the innate host defence. Historically, these immune cells have been considered to play a critical role in controlling the severity of influenza A virus (IAV) infection by limiting virus release, initiating local inflammatory responses and by priming subsequent adaptive immune responses. However, some IAV strains have been reported to replicate productively in human immune cells. Potential amplification and dissemination of IAV from immune cells may therefore be an important virulence determinant. Herein, we will review findings in relation to the fate of IAV following infection of MΦ and DC. Insights regarding the consequences and outcomes of IAV infection of airway MΦ and DC are discussed in order to gain a better understanding of the pathogenesis of influenza virus.

Abstract 586: CD40L on T Cells is a Major Contributor to Atherosclerosis in Hyperlipidemic Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Norbert Gerdes ◽  
Christina Buerger ◽  
Holger Winkels ◽  
Christian Weber ◽  
Esther Lutgens
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Chronic Inflammatory Disease ◽  
Chow Diet ◽  
Gene Markers ◽  
Anti Inflammatory

Atherosclerosis is a lipid driven chronic inflammatory disease of the arterial wall, involving both innate and adaptive immune responses. Specialized immune cells such as monocytes, B cells, T cells and dendritic cells (DCs) contribute to disease progression or control the inflammatory responses. The CD40-CD40L dyad was identified as an efficient modulator of cellular immune responses. CD40 is a member of the tumor necrosis factor receptor (TNFR) superfamily and is activated by CD40 ligand (CD40L). CD40 and CD40L both are expressed on the majority of immune and non-immune cells associated with atherosclerosis. However, the specific contribution of CD40-CD40L signaling on the different single cell types towards atherosclerosis progression remains undefined. Here, we aimed to investigate the cell type-specific mechanisms of CD40-CD40L interactions in atherosclerosis by generating mice with a conditional ablation of CD40L on T cells. Hyperlipidemic mice with a T cell-specific deficiency of CD40L developed significantly smaller atherosclerotic lesions in the ascending after 28 weeks of chow diet, and following 6 weeks of a cholesterol-enriched diet when compared to their littermate controls. Changes in lesion size were accompanied by a modified anti-inflammatory plaque phenotype, characterized by an increased proportion of smooth muscle cells and a reduced number of pro-inflammatory immune cells, such as macrophages and T cells. T cell CD40L-deficient mice displayed systematically reduced expression of pro-inflammatory cytokines such as IL-1β, IL-2, IL-12, and IFNγ, and increased expression of anti-inflammatory cytokines IL-10 and TGFβ. This anti-inflammatory milieu was paralleled a change in the development and activation status of the T cells with mice lacking CD40L on T cells displaying a reduction in the expression of cytokines and gene markers associated with the activation of T cells (e.g., IL-2, CD69). This change was also reflected within the T cell populations which had a reduced proportion of activated effector T cells and an increased ratio of naïve T cells. Thus, our study ascribes CD40L on T cells a central role in atherosclerosis.

Introduction to Clinical Immunology: Overview of the Immune Response, Autoimmune Conditions, and Immunosuppressive Therapeutics for Rheumatic Diseases

2016 ◽  
Author(s):  
Steven K. Lundy ◽  
Alison Gizinski ◽  
David A. Fox
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Cell ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Adaptive Immunity ◽  
Cell Populations ◽  
Hematopoietic Stem ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune

The immune system is a complex network of cells and mediators that must balance the task of protecting the host from invasive threats. From a clinical perspective, many diseases and conditions have an obvious link to improper functioning of the immune system, and insufficient immune responses can lead to uncontrolled acute and chronic infections. The immune system may also be important in tumor surveillance and control, cardiovascular disease, health complications related to obesity, neuromuscular diseases, depression, and dementia. Thus, a working knowledge of the role of immunity in disease processes is becoming increasingly important in almost all aspects of clinical practice. This review provides an overview of the immune response and discusses immune cell populations and major branches of immunity, compartmentalization and specialized immune niches, antigen recognition in innate and adaptive immunity, immune tolerance toward self antigens, inflammation and innate immune responses, adaptive immune responses and helper T (Th) cell subsets, components of the immune response that are important targets of treatment in autoimmune diseases, mechanisms of action of biologics used to treat autoimmune diseases and their approved uses, and mechanisms of other drugs commonly used in the treatment of autoimmune diseases. Figures show the development of erythrocytes, platelets, lymphocytes, and other immune system cells originating from hematopoietic stem cells that first reside in the fetal liver and later migrate to the bone marrow, antigen–major histocompatibility complex recognition by T cell receptor control of T cell survival and activation, and Th cells as central determinants of the adaptive immune response toward different stimuli. Tables list cell populations involved in innate and adaptive immunity, pattern recognition receptors with known ligands, autoantibody-mediated human diseases: examples of pathogenic mechanisms, selected Food and Drug Administration–approved autoimmune disease indications for biologics, and mechanism of action of biologics used to treat autoimmune diseases.   This review contains 3 highly rendered figures, 5 tables, and 64 references.

scholarly journals Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 372 ◽  
Author(s):  
Karl J. Harber ◽  
Kyra E. de Goede ◽  
Sanne G. S. Verberk ◽  
Elisa Meinster ◽  
Helga E. de Vries ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Phenotype ◽  
Independent Manner ◽  
Inflammatory Macrophages ◽  
Necrosis Factor

Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a lot of attention and emerged as a crucial regulator of macrophage responses and inflammation. Succinate was originally described as a metabolite that supports inflammation via distinct routes. Recently, studies have indicated that succinate and its receptor SUCNR1 can suppress immune responses as well. These apparent contradictory effects might be due to specific experimental settings and particularly the use of distinct succinate forms. We therefore compared the phenotypic and functional effects of distinct succinate forms and receptor mouse models that were previously used for studying succinate immunomodulation. Here, we show that succinate can suppress secretion of inflammatory mediators IL-6, tumor necrosis factor (TNF) and nitric oxide (NO), as well as inhibit Il1b mRNA expression of inflammatory macrophages in a SUCNR1-independent manner. We also observed that macrophage SUCNR1 deficiency led to an enhanced inflammatory response without addition of exogenous succinate. While our study does not reveal new mechanistic insights into how succinate elicits different inflammatory responses, it does indicate that the inflammatory effects of succinate and its receptor SUCNR1 in macrophages are clearly context dependent.

scholarly journals The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Lan Kang ◽  
Xiang Zhang ◽  
Liangliang Ji ◽  
Tiantian Kou ◽  
Sinead M. Smith ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Late Phase ◽  
Intestinal Immunity ◽  
Adaptive Immune Responses ◽  
Cell Lineages ◽  
Adaptive Immune ◽  
Intestinal Macrophage ◽  
Pathogen Clearance

Macrophages play pleiotropic roles in maintaining the balance between immune tolerance and inflammatory responses in the gut. Here, we identified transcription factor RBP-J as a crucial regulator of colonic macrophage–mediated immune responses against the enteric pathogen Citrobacter rodentium. In the immune response phase, RBP-J promoted pathogen clearance by enhancing intestinal macrophage-elicited Th17 cell immune responses, which was achieved by maintenance of C/EBPβ-dependent IL-6 production by overcoming miRNA-17∼92–mediated suppressive effects. RBP-J deficiency–associated phenotypes could be genetically corrected by further deleting miRNA-17∼92 in macrophages. In the late phase, noneradicated pathogens in RBP-J KO mice recruited abundant IL-1β–expressing CD64+Ly6C+ colonic macrophages and thereby promoted persistence of ILC3-derived IL-22 to compensate for the impaired innate and adaptive immune responses, leading to ultimate clearance of pathogens. These results demonstrated that colonic macrophage–intrinsic RBP-J dynamically orchestrates intestinal immunity against pathogen infections by interfacing with key immune cells of T and innate lymphoid cell lineages.

scholarly journals P01.10 IFNy secretion of adaptive and innate immune cells as a parameter to display leukaemia derived dendritic cell (DCleu) mediated immune responses in AML

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A13.1-A13
Author(s):  
LK Klauer ◽  
O Schutti ◽  
S Ugur ◽  
F Doraneh-Gard ◽  
N Rogers ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Immune Cells ◽  
Gm Csf ◽  
Adaptive Immune ◽  
Cik Cells ◽  
Adaptive Immune Cells ◽  
Suitable Parameter

BackgroundMyeloid leukaemic blasts can be converted into leukaemia derived dendritic cells (DCleu) with blastmodulatory Kit-I and Kit-M, which have the competence to regularly activate T and immunoreactive cells to gain anti-leukaemic activity or rather cytotoxicity. As innate and adaptive immune responses are notably promoted by the cytokine interferon gamma (IFNy), we hypothesised that the IFNy secretion could be a suitable parameter to display DC/DCleu mediated immunologic activity and even anti-leukaemic cytotoxicity.Materials and MethodsDC/DCleu were generated from leukaemic WB with Kit-I (GM-CSF + OK-432) and Kit-M (GM-CSF + PGE1) and used to stimulate T cell enriched immunoreactive cells. Initiated anti-leukaemic cytotoxicity was investigated with a cytotoxicity fluorolysis assay (CTX). Initiated IFNy secretion of innate and adaptive immune cells (T cells, TCD4+ cells, TCD8+ cells, NKCD56+ cells, NKCD161+ cells, CIKCD56+ cells, CIKCD161+ cells and iNKT) was investigated with a cytokine secretion assay (CSA). In some cases IFNy production was additionally evaluated with an intracellular cytokine assay (ICA). Conclusively, the IFNy secretion of immunoreactive cells was correlated with the anti-leukaemic cytotoxicity.ResultsSignificant amounts of DC and DCleu as well as migratory DC and DCleu could be generated with Kit-I and Kit-M without induction of blast proliferation. T cell enriched immunoreactive cells stimulated with DC/DCleu showed an increased anti-leukaemic cytotoxicity and an increased IFNy secretion of T, NK and CIK cells compared to control. Both the CSA and ICA yielded comparable amounts of IFNy positive innate and adaptive immune cells. The correlation between the IFNy secretion of immunoreactive cells and the anti-leukaemic cytotoxicity showed a positive relationship in T cells, TCD4+ cells, TCD8+ cells and NKCD56+ cells.ConclusionsWe found blastmodulatory Kit-I and Kit-M competent to generate DC/DCleu from leukaemic WB. Stimulation of T cell enriched immunoreactive cells with DC/DCleu regularly resulted in an increased anti-leukaemic cytotoxicity and an increased IFNy dependent immunological activity of T, NK and CIK cells compared to control. Moreover the anti-leukaemic cytotoxicity positively correlated with the IFNy secretion in T cells, TCD4+ cells, TCD8+ cells, NKCD56+ cells. We therefore consider the IFNy secretion of innate and adaptive immune cells to be a suitable parameter to assess the efficacy of in vitro and potentially in vivo AML immunotherapy. The CSA in this regard proved to be a convenient and reproducible technique to detect and phenotypically characterise IFNy secreting cells of the innate and adaptive immune system.Disclosure InformationL.K. Klauer: None. O. Schutti: None. S. Ugur: None. F. Doraneh-Gard: None. N. Rogers: None. M. Weinmann: None. D. Krämer: None. A. Rank: None. C. Schmid: None. B. Eiz-Vesper: None. H.M. Schmetzer: None.

scholarly journals Leukocyte Cathepsin C Deficiency Attenuates Atherosclerotic Lesion Progression by Selective Tuning of Innate and Adaptive Immune Responses

2015 ◽  
Vol 35 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Veronica Herías ◽  
Erik A.L. Biessen ◽  
Cora Beckers ◽  
Dianne Delsing ◽  
Mengyang Liao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Atherosclerotic Lesion ◽  
Adaptive Immune Responses ◽  
Cathepsin C ◽  
Adaptive Immune

β-Defensins: Linking Innate and Adaptive Immunity Through Dendritic and T Cell CCR6

Science ◽  
1999 ◽  
Vol 286 (5439) ◽  
pp. 525-528 ◽  
Author(s):  
D. Yang ◽  
O. Chertov ◽  
S. N. Bykovskaia ◽  
Q. Chen ◽  
M. J. Buffo ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cytoplasmic Membrane ◽  
Memory T Cells ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune ◽  
Microbial Invasion ◽  
Immature Dendritic Cells ◽  
Chemokine Ligand

Defensins contribute to host defense by disrupting the cytoplasmic membrane of microorganisms. This report shows that human β-defensins are also chemotactic for immature dendritic cells and memory T cells. Human β-defensin was selectively chemotactic for cells stably transfected to express human CCR6, a chemokine receptor preferentially expressed by immature dendritic cells and memory T cells. The β-defensin–induced chemotaxis was sensitive to pertussis toxin and inhibited by antibodies to CCR6. The binding of iodinated LARC, the chemokine ligand for CCR6, to CCR6-transfected cells was competitively displaced by β-defensin. Thus, β-defensins may promote adaptive immune responses by recruiting dendritic and T cells to the site of microbial invasion through interaction with CCR6.

scholarly journals Dendritic Cells under Hypoxia: How Oxygen Shortage Affects the Linkage between Innate and Adaptive Immunity

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Sandra Winning ◽  
Joachim Fandrey
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Mature Dendritic Cell ◽  
Innate And Adaptive Immunity ◽  
Cell Functions ◽  
Adaptive Immune ◽  
Oxygen Shortage

Dendritic cells (DCs) are considered as one of the main regulators of immune responses. They collect antigens, process them, and present typical antigenic structures to lymphocytes, thereby inducing an adaptive immune response. All these processes take place under conditions of oxygen shortage (hypoxia) which is often not considered in experimental settings. This review highlights how deeply hypoxia modulates human as well as mouse immature and mature dendritic cell functions. It tries to linkin vitroresults to actualin vivostudies and outlines how hypoxia-mediated shaping of dendritic cells affects the activation of (innate) immunity.

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