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ANIMATE SIGNED

Adaptive Immunity in Human Atherosclerosis: Understanding its Cellular Basis to Define Novel Immunomodulatory Therapies

Total Cost €

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EC-Contrib. €

0

Partnership

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 ANIMATE project word cloud

Explore the words cloud of the ANIMATE project. It provides you a very rough idea of what is the project "ANIMATE" about.

autoimmune    antigens    narrowing    dimension    vivo    multimers    plaques    therapeutically    causes    tools    stroke    functional    inferred    mouse    anti    framework    chronic    patients    regulatory    apob    ldl    vessel    rna    scrna    mhc    cellular    cytometry    cytof    imaging    pathogenic    cholesterol    immunomodulatory    acute    pool    recognize    course    correlation    transformation    helper    blockade    atherosclerotic    immune    share    reactive    anticipated    complications    density    self    phenotypes    lineage    function    elusive    insights    mass    inflammatory    cd4    decipher    cells    association    pro    atherosclerosis    natural    accompanied    stabilize    death    strategies    live    tested    indirect    infarction    antigen    unclear    effector    conceptual    vaccination    auto    protein    transform    data    temporal    disease    sequencing    spatial    detect    worldwide    seq    transfers    cytokine    atheroprotective    adoptive    explore    preliminary    tracing    map    therapeutic    cell    clinical    suggest    immunity    existence    protective    single    population    prevent    arteries    employs    myocardial    traits    lipoprotein    direct    models   

Project "ANIMATE" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAETSKLINIKUM FREIBURG 

Organization address
address: HUGSTETTER STRASSE 49
city: FREIBURG
postcode: 79106
website: n.a.

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 1˙499˙946 €
 EC max contribution 1˙499˙946 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-01-01   to  2024-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAETSKLINIKUM FREIBURG DE (FREIBURG) coordinator 1˙499˙946.00

Map

 Project objective

Atherosclerosis is a chronic immune disease of arteries that causes vessel-narrowing atherosclerotic plaques. Its acute complications, myocardial infarction and stroke, are the leading causes of death worldwide. Atherosclerosis is accompanied by an inflammatory and autoimmune response with CD4 T-helper cells that recognize self-antigens, including ApoB-100 (ApoB), the main protein in low-density lipoprotein (LDL) cholesterol. Although their existence has been inferred from indirect evidence, the existence and function of atherosclerosis-specific, self-reactive CD4 T cells on a single-cell level remains elusive. In particular, it is unclear whether these are pro- or anti-inflammatory. Preliminary data suggest the existence of a natural pool of ApoB-reactive T-helper cells that share properties with atheroprotective T-regulatory cells but transform into pathogenic T-effector cells in the natural course of disease. This proposal aims to explore this loss of protective immunity on a cellular and function level. It employs novel tools to detect antigen-specific T cells in vivo by MHC-II multimers, mass cytometry (CyTOF), single cell RNA-sequencing (scRNA-seq), lineage-tracing mouse models, and live cell imaging. Based on the anticipated findings, this study will define a map of auto-reactive T-helper cell phenotypes in a temporal, spatial, and functional dimension. These insights will be used to identify novel immunomodulatory strategies to therapeutically stabilize the population of protective ApoB-specific T-helper cells, or to prevent their transformation into pathogenic T cell phenotypes by adoptive cells transfers, vaccination, or cytokine-blockade. In clinical association studies, a direct correlation of auto-immunity and clinical atherosclerosis will be tested. This proposal will decipher traits of protective immunity in atherosclerosis and help to build the conceptual framework to define novel therapeutic strategies for patients.

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