Innovating Works

T_CELL(S)_DIFFER

Financiado
Differentiation of pro inflammatory T cell subsets in vivo
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 caus... 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-(IFN-) 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+ cells, and NKT cells – to global Th1 or Th17 immune responses, using various tools including a IFN-/IL-17 double reporter mouse. Importantly, we will study Th1/ Th17 differentiation in vivo, inmodels of infection with Plasmodium berghei or Mycobacterium tuberculosis. We will analyse theindividual and combined contributions of the distinct T cell subsets, their cellular interactions andpotential interdependence in lymphoid organs and in target organs of infection. We further envisage a molecular understanding of how innate (and NKT) and adaptive (CD4+ and CD8+) T cell subsets acquire their respective capacities to produce IFN-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-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 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. ver más
30/06/2015
iMM
2M€

Línea de financiación: concedida

El organismo FP7 notifico la concesión del proyecto el día 2015-06-30
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANT... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5