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IMSTREV

Immune modulation by lymph node stromal cell-derived extracellular vesicles

Total Cost €

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EC-Contrib. €

0

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.

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

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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