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A novel physiological role for IRE1 and RIDD..., maintaining the balance between tolerance and immunity?

Total Cost €


EC-Contrib. €






 DCRIDDLE project word cloud

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

team    murine    functions    autoimmune    upr    cdc1s    fundamental    dc    infection    dcs    immunogenic    gatekeepers    clearance    versus    autoimmunity    apoptotic    signaling    protein    association    balances    puzzling    active    danger    cells    balance    immunity    unfolded    axis    yield    line    disease    hypothesize    shift    questions    setting    illusive    models    stage    candidate    tolerogenic    switch    branches    presentation    viral    protective    cell    found    endoplasmic    orchestrating    entails    graft    biology    insights    stretch    chronic    overt    paradigm    physiological    function    host    stress    xbp1    signature    immune    link    tolerance    constitutively    data    antigens    er    metabolic    ire1    diseases    conserved    tumor    steady    self    maturation    activated    entirely    branch    determines    disturbed    reticulum    reveals    envisage    discovered    hitherto    dissect    unanticipated    play    vivo    dendritic    thereby    gwas    genome    gene    immunology    preliminary    antigen    signs   

Project "DCRIDDLE" data sheet

The following table provides information about the project.


Organization address
postcode: 9052

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 Belgium [BE]
 Total cost 1˙999˙196 €
 EC max contribution 1˙999˙196 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-COG
 Funding Scheme ERC-COG
 Starting year 2019
 Duration (year-month-day) from 2019-02-01   to  2024-01-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VIB VZW BE (ZWIJNAARDE - GENT) coordinator 1˙999˙196.00


 Project objective

Dendritic cells (DCs) play a crucial role as gatekeepers of the immune system, coordinating the balance between protective immunity and tolerance to self antigens. What determines the switch between immunogenic versus tolerogenic antigen presentation remains one of the most puzzling questions in immunology. My team recently discovered an unanticipated link between a conserved stress response in the endoplasmic reticulum (ER) and tolerogenic DC maturation, thereby setting the stage for new insights in this fundamental branch in immunology. Specifically, we found that one of the branches of the unfolded protein response (UPR), the IRE1/XBP1 signaling axis, is constitutively active in murine dendritic cells (cDC1s), without any signs of an overt UPR gene signature. Based on preliminary data we hypothesize that IRE1 is activated by apoptotic cell uptake, orchestrating a metabolic response from the ER to ensure tolerogenic antigen presentation. This entirely novel physiological function for IRE1 entails a paradigm shift in the UPR field, as it reveals that IRE1’s functions might stretch far from its well-established function induced by chronic ER stress. The aim of my research program is to establish whether IRE1 in DCs is the hitherto illusive switch between tolerogenic and immunogenic maturation. To this end, we will dissect its function in vivo both in steady-state conditions and in conditions of danger (viral infection models). In line with our data, IRE1 has recently been identified as a candidate gene for autoimmune disease based on Genome Wide Association Studies (GWAS). Therefore, I envisage that my research program will not only have a large impact on the field of DC biology and apoptotic cell clearance, but will also yield new insights in diseases like autoimmunity, graft versus host disease or tumor immunology, all associated with disturbed balances between tolerogenic and immunogenic responses.

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The information about "DCRIDDLE" are provided by the European Opendata Portal: CORDIS opendata.

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