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TWILIGHT SIGNED

ToWards Immunisations that Last: the Immunology and Gerontology of Helper T cells

Total Cost €

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EC-Contrib. €

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Partnership

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 TWILIGHT project word cloud

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

suppress    medical    vaccine    helper    mechanisms    human    structure    lived    hypotheses    healthy    memory    mouse    plasma    life    rendering    older    date    age    aberrant    creates    specialised    microenvironment    fulfil    models    susceptible    morbidity    tissue    function    infections    ambition    reducing    accomplishment    tfr    senescent    decline    understand    secondary    people    inducing    society    generates    modify    secreting    complexity    attempts    intricate    hypothesise    vaccination    accumulation    lymphoid    individuals    biology    innovative    extension    impaired    cd4    opposition    centre    science    ageing    gc    infection    unknown    regulatory    modern    expectancy    alters    act    antibody    efficacy    germinal    immune    immunity    strikingly    expectation    hindered    molecular    respectively    responsible    cellular    dependent    prominent    tfh    cells    protective    follicular    declines    impairing    underlying    uncover    benefit    tissues   

Project "TWILIGHT" data sheet

The following table provides information about the project.

Coordinator
THE BABRAHAM INSTITUTE 

Organization address
address: Babraham Hall
city: CAMBRIDGE
postcode: CB22 3AT
website: www.babraham.ac.uk

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 United Kingdom [UK]
 Total cost 1˙499˙997 €
 EC max contribution 1˙499˙997 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-06-01   to  2020-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE BABRAHAM INSTITUTE UK (CAMBRIDGE) coordinator 1˙499˙997.00

Map

 Project objective

A major accomplishment of modern society is the extension of human life expectancy. However, this creates a new challenge for medical science, to facilitate healthy ageing. With age, the function of the immune system declines, rendering older people more susceptible to infections and less able to benefit from vaccination. Indeed, improving vaccine efficacy is key to reducing infection-related morbidity in older people. To date, the complexity of the ageing process has hindered attempts to fulfil this ambition, and thus innovative approaches are required to better understand the underlying biology.

Vaccination creates protective immunity by inducing the germinal centre (GC) response, an intricate process that generates memory B cells and long-lived antibody-secreting plasma cells. However, the GC response declines with age. Strikingly, it is not B cells that are responsible for the age-dependent decline in the GC response, but the CD4 T cells and the microenvironment of older individuals. The cellular and molecular mechanisms responsible, however, remain unknown. In the GC there are two subsets of specialised CD4 T cells, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells, which act in opposition to promote and suppress the response, respectively. I hypothesise that aberrant formation and/or function of Tfh and Tfr cells contribute to impaired GC responses during ageing, and that these cells could be targeted to improve vaccine efficacy. Furthermore, the most prominent age-dependent change in secondary lymphoid tissues is the accumulation of senescent cells, which can modify immune function and tissue structure. I hypothesise that accumulation of senescent cells alters this microenvironment, impairing the response to vaccination. I will test these hypotheses using new mouse models and innovative approaches to human research, in the expectation that the knowledge obtained will promote healthy ageing and uncover novel aspects of GC biology.

 Publications

year authors and title journal last update
List of publications.
2020 Ine Vanderleyden, Sigrid C. Fra-Bido, Silvia Innocentin, Marisa Stebegg, Hanneke Okkenhaug, Nicola Evans-Bailey, Wim Pierson, Alice E. Denton, Michelle A. Linterman
Follicular Regulatory T Cells Can Access the Germinal Center Independently of CXCR5
published pages: 611-619.e4, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.12.076
Cell Reports 30/3 2020-02-04
2019 Danika L. Hill, Wim Pierson, Daniel J. Bolland, Catherine Mkindi, Edward J. Carr, Jiong Wang, Sophie Houard, Steven W. Wingett, Regine Audran, Elizabeth F. Wallin, Said A. Jongo, Kassim Kamaka, Martin Zand, Francois Spertini, Claudia Daubenberger, Anne E. Corcoran, Michelle A. Linterman
The adjuvant GLA-SE promotes human Tfh cell expansion and emergence of public TCRβ clonotypes
published pages: 1857-1873, ISSN: 0022-1007, DOI: 10.1084/jem.20190301
The Journal of Experimental Medicine 216/8 2020-01-29
2019 Marisa Stebegg, Alyssa Silva-Cayetano, Silvia Innocentin, Timothy P. Jenkins, Cinzia Cantacessi, Colin Gilbert, Michelle A. Linterman
Heterochronic faecal transplantation boosts gut germinal centres in aged mice
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-10430-7
Nature Communications 10/1 2020-01-29
2017 Louise M. C. Webb, Michelle A. Linterman
Signals that drive T follicular helper cell formation
published pages: 185-194, ISSN: 0019-2805, DOI: 10.1111/imm.12778
Immunology 152/2 2019-05-29
2017 Valter R. Fonseca, Ana Agua-Doce, Ana Raquel Maceiras, Wim Pierson, Filipa Ribeiro, Vasco C. Romão, Ana Rita Pires, Susana Lopes da Silva, João Eurico Fonseca, Ana E. Sousa, Michelle A. Linterman, Luis Graca
Human blood T fr cells are indicators of ongoing humoral activity not fully licensed with suppressive function
published pages: eaan1487, ISSN: 2470-9468, DOI: 10.1126/sciimmunol.aan1487
Science Immunology 2/14 2019-05-29
2016 Michelle A. Linterman, Danika L. Hill
Can follicular helper T cells be targeted to improve vaccine efficacy?
published pages: , ISSN: 2046-1402, DOI: 10.12688/f1000research.7388.1
F1000Research 2019-05-27
2016 Meryem Aloulou, Edward J. Carr, Mylène Gador, Alexandre Bignon, Roland S. Liblau, Nicolas Fazilleau, Michelle A. Linterman
Follicular regulatory T cells can be specific for the immunizing antigen and derive from naive T cells
published pages: 10579, ISSN: 2041-1723, DOI: 10.1038/ncomms10579
Nature Communications 7 2019-05-27
2016 Edward J Carr, James Dooley, Josselyn E Garcia-Perez, Vasiliki Lagou, James C Lee, Carine Wouters, Isabelle Meyts, An Goris, Guy Boeckxstaens, Michelle A Linterman, Adrian Liston
The cellular composition of the human immune system is shaped by age and cohabitation
published pages: 461-468, ISSN: 1529-2908, DOI: 10.1038/ni.3371
Nature Immunology 17/4 2019-05-27

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