Explore the words cloud of the TWILIGHT project. It provides you a very rough idea of what is the project "TWILIGHT" about.
The following table provides information about the project.
THE BABRAHAM INSTITUTE
|Coordinator Country||United Kingdom [UK]|
|Total cost||1˙499˙997 €|
|EC max contribution||1˙499˙997 € (100%)|
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
|Duration (year-month-day)||from 2015-06-01 to 2020-05-31|
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|1||THE BABRAHAM INSTITUTE||UK (CAMBRIDGE)||coordinator||1˙499˙997.00|
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.
|year||authors and title||journal||last update|
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|
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 TCRÎ² clonotypes
published pages: 1857-1873, ISSN: 0022-1007, DOI: 10.1084/jem.20190301
|The Journal of Experimental Medicine 216/8||2020-01-29|
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|
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
Valter R. Fonseca, Ana Agua-Doce, Ana Raquel Maceiras, Wim Pierson, Filipa Ribeiro, Vasco C. RomÃ£o, Ana Rita Pires, Susana Lopes da Silva, JoÃ£o 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|
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
Meryem Aloulou, Edward J. Carr, MylÃ¨ne 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|
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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