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

Descrizione del progetto

Aumentare l’efficacia dei vaccini nelle popolazioni che invecchiano

Nel corso degli anni la diminuzione di molte malattie infettive e dei relativi decessi può essere attribuita all’impatto significativo delle vaccinazioni. Tuttavia, con l’avanzare dell’età, il sistema immunitario delle persone si indebolisce, rendendole più vulnerabili alle infezioni e meno capaci di beneficiare dei vaccini. Si tratta di un fenomeno irreversibile o è possibile migliorare la risposta alla vaccinazione? Il progetto TWILIGHT, finanziato dal Consiglio europeo della ricerca, mira a comprendere i meccanismi alla base di questo declino e a elaborare strategie per migliorare l’efficacia della vaccinazione. I ricercatori studieranno i linfociti T e le cellule presentanti l’antigene negli individui anziani per decifrare i meccanismi cellulari e molecolari responsabili della risposta subottimale al vaccino.

Obiettivo

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.

Meccanismo di finanziamento

ERC-STG - Starting Grant

Coordinatore

THE BABRAHAM INSTITUTE
Contribution nette de l'UE
€ 1 499 997,95
Indirizzo
Babraham hall
CB22 3AT Cambridge
Regno Unito

Mostra sulla mappa

Regione
East of England East Anglia Cambridgeshire CC
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 1 499 997,95

Beneficiari (1)