T_CELL(S)_DIFFER
Differentiation of pro-inflammatory T cell subsets in vivo
| Coordinatore | INSTITUTO DE MEDICINA MOLECULAR
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | Portugal [PT] |
| Totale costo | 1˙500˙000 € |
| EC contributo | 1˙500˙000 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2010-StG_20091118 |
| Funding Scheme | ERC-SG |
| Anno di inizio | 2010 |
| Periodo (anno-mese-giorno) | 2010-12-01 - 2015-11-30 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
INSTITUTO DE MEDICINA MOLECULAR
Organization address
address: AVENIDA PROF EGAS MONIZ contact info |
PT (LISBOA) | hostInstitution | 1˙500˙000.00 |
| 2 |
INSTITUTO DE MEDICINA MOLECULAR
Organization address
address: AVENIDA PROF EGAS MONIZ contact info |
PT (LISBOA) | hostInstitution | 1˙500˙000.00 |
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Obiettivo del progetto (Objective)
'Our understanding of T cell differentiation impacts on vaccine development and on the treatment of (auto) immune disorders. T cells are key players in inflammation, a crucial component of the immune response to pathogens that causes severe damage to the host when uncontrolled. The cytokines Interferon-ï§ï€ (IFN-ï§) and Interleukin-17 (IL-17) are critical mediators of the proinflammatory activity of T cells usually designated as “T helper 1” (Th1) and Th17, respectively. Here we propose to investigate the contribution of all T cell lineages - CD4 and CD8 ï¡ï¢ï€ cells, ï§ï¤ï€ and NKT cells – to global Th1 or Th17 immune responses, using various tools including a IFN-ï§/ï€ IL-17 double reporter mouse. Importantly, we will study Th1/ Th17 differentiation in vivo, inï€ models of infection with Plasmodium berghei or Mycobacterium tuberculosis. We will analyse theï€ individual and combined contributions of the distinct T cell subsets, their cellular interactions andï€ potential interdependence in lymphoid organs and in target organs of infection. We further envisage a molecular understanding of how innate (ï§ï¤ï€ and NKT) and adaptive (CD4 and CD8) T cell subsets acquire their respective capacities to produce IFN-ï§ï€ or IL-17 in vivo. We will dissect (pre-/ post-) transcriptional mechanisms of regulation of Ifng and Il17 expression in the various T cell subsets, ultimately at the single-cell level. We aim at characterizing networks of transcription factors and microRNAs that regulate Th1/ Th17 differentiation either in all or in specific T cell subsets. We are particularly interested in addressing the constitutive expression of IFN-ï§ï€ or IL-17 by innate T lymphocytes, which is set up in the thymus. We will define the molecular components of this “developmental pre-programming” of ï§ï¤ï€ and NKT cells in comparison with the mechanisms of peripheral induction of CD4 Th1/ Th17 cell differentiation upon infection. By contrast to the generalized focus on CD4 T cells, this project will consider Th1/ Th17 differentiation of all T cell lineages and their in vivo contributions to relevant models of infection. I believe this holistic view of organism-based immune parameters and their underlying molecular mechanisms, down to the single-cell level, will significantly advance our understanding of how the Immune System works.'