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ThymusTolerance SIGNED

Delineation of molecular mechanisms underlying the establishment and breakdown of immunological tolerance in the thymus

Total Cost €

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EC-Contrib. €

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Partnership

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 ThymusTolerance project word cloud

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

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Project "ThymusTolerance" data sheet

The following table provides information about the project.

Coordinator
WEIZMANN INSTITUTE OF SCIENCE 

Organization address
address: HERZL STREET 234
city: REHOVOT
postcode: 7610001
website: www.weizmann.ac.il

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 Israel [IL]
 Total cost 2˙220˙000 €
 EC max contribution 2˙220˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-09-01   to  2022-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    WEIZMANN INSTITUTE OF SCIENCE IL (REHOVOT) coordinator 2˙220˙000.00

Map

 Project objective

Central tolerance is shaped in the thymus, a primary lymphoid organ, where immature T lymphocytes are “educated” into mature cells, capable of recognizing foreign antigens, while tolerating the body’s own components. This process is driven mainly by two separate lineages of thymic epithelial cells (TECs), the cortical (cTEC) and the medullary (mTEC). While cTECs are critical at the early stages of T cell development, mTECs play a pivotal role in negative selection of self-reactive thymocytes and the generation of Foxp3 regulatory T (Treg) cells. Crucial to the key role of mTECs in the screening of self-reactive T cell clones, is their unique capacity to promiscuously express and present almost all self-antigens, including thousands of tissue-specific antigen (TSA) genes. Strikingly, the expression of most of this TSA repertoire in mTECs is regulated by a single transcriptional regulator called Aire. Indeed, Aire deficiency in mice and human patients results to multi-organ autoimmunity. Although there has been dramatic progress in our understanding of how thymic epithelial cells shape and govern the establishment of adaptive immunity and of immunological self-tolerance, there are still several outstanding questions with no comprehensive answers. Therefore, in the research proposed herein, we wish to provide more comprehensive answers to these still elusive, but very fundamental questions. Specifically we will aim at: 1.) Delineation of molecular mechanisms controlling TEC development and thymus organogenesis; 2.) Delineation of molecular mechanisms underlying promiscuous gene expression in the thymus; 3.) Identification and characterization of molecular determinants responsible for the breakdown of thymus-dependent self-tolerance. To this end, we will build upon our recently published data, as well as unpublished preliminary data and utilize several state-of-the-art and interdisciplinary approaches, which have become an integral part of our lab’s toolbox.

 Publications

year authors and title journal last update
List of publications.
2017 Ayelet Avin, Maayan Levy, Ziv Porat, Jakub Abramson
Quantitative analysis of protein-protein interactions and post-translational modifications in rare immune populations
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-01808-6
Nature Communications 8/1 2019-06-06
2018 Chamutal Bornstein, Shir Nevo, Amir Giladi, Noam Kadouri, Marie Pouzolles, François Gerbe, Eyal David, Alice Machado, Anna Chuprin, Beáta Tóth, Ori Goldberg, Shalev Itzkovitz, Naomi Taylor, Philippe Jay, Valérie S. Zimmermann, Jakub Abramson, Ido Amit
Single-cell mapping of the thymic stroma identifies IL-25-producing tuft epithelial cells
published pages: 622-626, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0346-1
Nature 559/7715 2019-06-06
2019 Shir Nevo, Noam Kadouri, Jakub Abramson
Tuft cells: From the mucosa to the thymus
published pages: 1-9, ISSN: 0165-2478, DOI: 10.1016/j.imlet.2019.02.003
Immunology Letters 210 2019-06-06
2017 Jakub Abramson, Graham Anderson
Thymic Epithelial Cells
published pages: 85-118, ISSN: 0732-0582, DOI: 10.1146/annurev-immunol-051116-052320
Annual Review of Immunology 35/1 2019-06-06

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