TREG · Analysis of regulatory T cell proliferation and apoptosis in vivo at the cellular and molecular level
FP7 — People (Marie Curie Actions)
- Duration
- 2010-06-01 → 2014-05-31
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-IRG
Lines connect the coordinator with its partners.
Results in brief
Analysis of regulatory T cell proliferation and apoptosis in vivo at the cellular and molecular level
Progress towards objectives - Aim 1. To characterise the cellular properties of Foxp3+ regulatory T cells in regards to homeostasis, proliferation and apoptosis (Period 1) - Aim 2. To test the role of Bcl-2 family members in controlling the proliferative and apoptotic properties of Foxp3+ regulatory T cells (Period 2) - Aim 3. To test the role of the Pdl / IL-2 axis in modulating Foxp3+ regulatory T cell numbers during inflammation (Period 2) Description of work performed - Foxp3DTR/Thy1.1 system setup and optimised - Kinetics of regulatory T cell reconstitution measured - Contribution of proliferation and apoptosis to regulatory T cell reconstitution measured - Role of Bcl2, BclX, Mcl1 in regulatory T cell homeostasis assessed - Role of Bim, Bak/Bad in regulatory T cell homeostasis assessed - Role of dendritic cells, IL-2 and costimulation in regulatory T cell homeostasis assessed - Construct and mice for IL2 over-expression generated Description of main results - Identification of Mcl1 as the primary factor for regulatory T cell homeostasis - Determination that Bcl2 and BclX play little role in regulatory T cell homeostasis - Identification of Bak/Bax as key regulators of regulatory T cell number - Identification of Bim as key regulators of regulatory T cell number - Identification of costimulation, but not dendritic cells, as key regulators of regulatory T cell homeostasis - Identification of IL-2 effect on Mcl1 and survival - Analysis of kinetics of regulatory T cell response to disturbed homeostasis Potential impact - Aid in the future design of therapeutics to alter regulatory T cell number. Patent submitted for gene-therapy use - Eg identification of Mcl1 as key drug target. Patent submitted for gene-therapy use - Development would have large impact on patients with autoimmune disease
Data: CORDIS, © European Union
Project objective
Foxp3+ regulatory T cells are critical for controlling the degree of immune activation during infection, autoimmunity and allergy. Despite the importance of this cell lineage to human health, relatively little is known about the molecular and cellular control of their differentiation and homeostasis. In order to rectify this deficit we propose to investigate the properties of proliferation and apoptosis during expansion, contraction and homeostatic stages, using sophisticated genetic models. We will also investigate the role of Bcl-2 family member genes and the IL2 / Pdl1 axis in the molecular control over these cellular properties. By dissecting the factors controlling regulatory T cell numbers we ultimately seek routes to make this process amenable to therapeutic manipulation.
Original text from CORDIS.
Participants
- VIB VZW · ZWIJNAARDE - GENTCoordinatorBelgium
Links
Data: CORDIS, © European Union