TREG SUPPRESSION
Deciphering the molecular basis of regulatory T cell suppression
| Coordinatore | KAROLINSKA INSTITUTET
Organization address
address: Nobels Vag 5 contact info |
| Nazionalità Coordinatore | Sweden [SE] |
| Totale costo | 100˙000 € |
| EC contributo | 100˙000 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-IRG-2008 |
| Funding Scheme | MC-IRG |
| Anno di inizio | 2009 |
| Periodo (anno-mese-giorno) | 2009-09-01 - 2013-08-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
KAROLINSKA INSTITUTET
Organization address
address: Nobels Vag 5 contact info |
SE (STOCKHOLM) | coordinator | 100˙000.00 |
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Obiettivo del progetto (Objective)
'Regulatory T cells (TREG) comprise a subset of CD4 T cells that maintain immunological tolerance by suppressing immune activation in a dominant manner. TREG helps shaping the immune responses to autoantigens, alloantigens, tumors, pathogens and allergens, and are thus considered a therapeutical target in a large variety of diseases. One aspect of TREG biology that remains poorly understood is what molecular program(s) are induced in cells that are being actively suppressed by TREG. The specific aims described below are designed to provide a better understanding of the molecular changes that occur as a result of TREG-mediated suppression and determine if the biochemical pathways altered by TREG-mediated suppression can be exploited for therapeutical purposes.
1. Characterize the molecular changes that occur in CD4 T cells and dendritic cells that are being suppressed by TREG using gene profiling and cell signaling experimental approaches.
2. Evaluate the importance and therapeutical potential of genes with an expression profile altered by TREG-mediated suppression in animal models of human diseases.'
Introduzione (Teaser)
A European study worked on the molecular basis of immune suppression with the aim of translating the results into therapeutic interventions.
Descrizione progetto (Article)
Our bodies fight against foreign substances including microorganisms via the immune system. Under normal situations, immune cells are taught to distinguish between foreign and self-antigens. Central to this immunological tolerance are a population of T lymphocytes, known as regulatory T cells (Tregs).
Although many aspects of Treg cell biology have been extensively studied, it remains to be determined what molecular changes occur in the cells that are being suppressed. In this context, the EU-funded 'Deciphering the molecular basis of regulatory T cell suppression' (TREG SUPPRESSION) project set out to characterise the molecular events that take place in CD4 T cells and dendritic cells, which are essentially the Treg targets.
Researchers had previously shown that the suppressive activity of Tregs can be passed on to naive T cells through cell contact, implicating transforming growth factor (TGF)-beta signalling. During the TREG SUPPRESSION project, they extended this work and elucidated the pathway components that are activated following suppression by Tregs.
Results revealed that deletion of the downstream inhibitor of TGF-beta signalling Smad 7 could induce atherosclerosis in transgenic mice. These atherosclerotic lesions were reduced upon transfer of Tregs, clearly indicating that Treg function through TGF-beta signalling is crucial for controlling inflammation.
Adaptive transfer of Tregs in a clinical setting will be explored next in patients suffering from inflammatory disorders. Additionally, the findings of the project have triggered research into the inhibition of Treg cell function as a means of amplifying anti-cancer immune responses.