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PREG-LAB SIGNED

Distinctive characterization of regulatory plasma cells and pro-inflammatory B cells in immunity: their origins, molecular properties, and cellular fates.

Total Cost €

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EC-Contrib. €

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Partnership

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 PREG-LAB project word cloud

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

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Project "PREG-LAB" data sheet

The following table provides information about the project.

Coordinator
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE 

Organization address
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.fr

contact info
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surname: n.a.
function: n.a.
email: n.a.
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fax: n.a.

 Coordinator Country France [FR]
 Total cost 1˙999˙375 €
 EC max contribution 1˙999˙375 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE FR (PARIS) coordinator 1˙918˙125.00
2    Deutsches Rheuma-Forschungszentrum Berlin DE (Berlin) participant 81˙250.00

Map

 Project objective

B cells can act both as negative regulators and as drivers of immunity through the production of cytokines. Through secretion of interleukin (IL)-10 B cells inhibited immunity in autoimmune and infectious diseases. For instance, IL-10 from B cells drove complete recovery from disease in experimental autoimmune encephalomyelitis (EAE), the primary animal model for multiple sclerosis (MS), while a lack of IL-10 production by B cells resulted in a severe chronic EAE. B cells can also suppress immunity via IL-35. Human B cells might similarly play inhibitory roles. In few patients with immune-mediated diseases B cell depletion therapy with Rituximab was associated with exacerbation of symptoms, or onset of new pathologies. Conversely, an opposite role of B cells as drivers of immunity was highlighted by the beneficial effect of Rituximab in some patients with rheumatoid arthritis or MS. Clinical improvement often precedes reduction in autoantibody levels in Rituximab treated patients, indicating that B cell-mediated pathogenesis is largely antibody-independent. A candidate factor for the deleterious effects of B cells in MS is IL-6. IL-6 secretion is a major mechanism of B cell-mediated pathogenesis in EAE, and B cells from MS patients produced more IL-6 than cells from healthy individuals. There is now an urgent need for the characterization of the phenotypes of the B cells producing IL-6, IL-10, and IL-35 in vivo at single cell and molecular levels. Markers for these cells might allow understanding the paradoxical effects of B cell-depletion therapy, and guide the development of novel agents depleting distinctively pro-inflammatory B cells, while sparing the remaining of the B cell compartment. Using advanced genetic models to identify and track cytokine-expressing cells, our project aims at characterizing B cells with pro- and anti-inflammatory functions in mice in vivo, to subsequently guide the identification of comparable markers in human.

 Publications

year authors and title journal last update
List of publications.
2018 Simon Fillatreau
B cells and their cytokine activities implications in human diseases
published pages: 26-31, ISSN: 1521-6616, DOI: 10.1016/j.clim.2017.07.020
Clinical Immunology 186 2019-04-03
2018 Andreia C. Lino, Van Duc Dang, Vicky Lampropoulou, Anna Welle, Jara Joedicke, Jelka Pohar, Quentin Simon, Jessie Thalmensi, Aurelia Baures, Vinciane Flühler, Imme Sakwa, Ulrik Stervbo, Stefanie Ries, Luc Jouneau, Pierre Boudinot, Takeshi Tsubata, Takahiro Adachi, Andreas Hutloff, Thomas Dörner, Ursula Zimber-Strobl, Alex F. de Vos, Katja Dahlke, Gunnar Loh, Sarantis Korniotis, Christian Goosmann, Jean-Claude Weill, Claude-Agnès Reynaud, Stefan H.E. Kaufmann, Jörn Walter, Simon Fillatreau
LAG-3 Inhibitory Receptor Expression Identifies Immunosuppressive Natural Regulatory Plasma Cells
published pages: 120-133.e9, ISSN: 1074-7613, DOI: 10.1016/j.immuni.2018.06.007
Immunity 49/1 2019-04-03

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