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IMSTREV

Immune modulation by lymph node stromal cell-derived extracellular vesicles

Total Cost €

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EC-Contrib. €

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Partnership

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 IMSTREV project word cloud

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

inducing    anticipates    cellular    candidate    differences    attributed    generation    decipher    interactions    formally    spectrometry    discriminate    immortalized    crispr    secreted    shown    critical    tools    pln    mln    nodes    mass    intestinal    inflammatory    periphery    cas9    newly    pathogens    immune    gut    edited    microbiota    cells    na    imprinted    mucosa    tested    subcellular    microenvironment    rna    dynamic    lymph    tregs    gaining    tolerance    mesenteric    stromal    treat    vaccine    modulate    modulatory    lns    mechanisms    soluble    intercellular    therapeutic    iuml    proof    skin    special    genome    frcs    preliminary    emphasis    molecular    laid    mediate    regulatory    draining    differentiation    seq    site    suggest    primarily    peripheral    commensal    fibroblastic    extracellular    ve    commensals    ln    homeostasis    molecules    data    maintenance    accordingly    thymus    display    autoimmune    diseases    details    evs    chronic    capacity    reticular    communication    treg    functional    vesicles   

Project "IMSTREV" data sheet

The following table provides information about the project.

Coordinator
HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH 

Organization address
address: INHOFFENSTRASSE 7
city: BRAUNSCHWEIG
postcode: 38124
website: www.helmholtz-hzi.de

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]
 Project website http://www.helmholtz-hzi.de/exim
 Total cost 171˙460 €
 EC max contribution 171˙460 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2015
 Duration (year-month-day) from 2015-07-01   to  2017-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH DE (BRAUNSCHWEIG) coordinator 171˙460.00

Map

 Project objective

Regulatory T cells (Tregs) are essential for maintenance of immune homeostasis and peripheral tolerance. The unique challenge to discriminate between pathogens and commensals requires the dynamic adaptation of Tregs to the microenvironment, particularly in the intestinal mucosa. Accordingly, although Tregs are primarily generated in the thymus, they can be also generated in the periphery, and gut-draining mesenteric lymph nodes (mLN) were shown to display a higher Treg-inducing capacity compared to skin-draining peripheral LNs (pLN). Our previous data suggest that these site-specific functional differences of LNs can be attributed to fibroblastic reticular stromal cells (FRCs), and the high Treg-inducing capacity of mLN can be imprinted in LN stromal cells by commensal microbiota. To decipher the molecular details of these site-specific immune-modulatory differences we generated immortalized FRCs, and preliminary data suggest that soluble factors secreted by mLN-derived FRCs mediate the high Treg-inducing capacity of mLN. The present proposal aims to identify molecules secreted from mLN-FRCs that modulate the differentiation of naïve T cells into Tregs. Special emphasis will be laid on the novel field of intercellular communication by extracellular vesicles (EVs), and both RNA-Seq and mass spectrometry approaches will be applied to identify the critical factors on a molecular level. To formally proof the functional importance of the newly identified candidate molecules, immortalized FRCs will be genome-edited using CRISPR-Cas9 technology and tested for their Treg-inducing capacity. Gaining insight into the cellular-subcellular interactions and major molecular mechanisms of peripheral tolerance and Treg generation anticipates promising tools for future vaccine development and therapeutic applications to treat chronic inflammatory and autoimmune diseases.

 Publications

year authors and title journal last update
List of publications.
2017 Maria Pasztoi, Joern Pezoldt, Michael Beckstette, Christoph Lipps, Dagmar Wirth, Manfred Rohde, Krisztina Paloczi, Edit Iren Buzas, Jochen Huehn
Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3 + regulatory T cells
published pages: , ISSN: 0014-2980, DOI: 10.1002/eji.201746960
European Journal of Immunology 2019-07-23

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