TREGinAD · Role of Aβ Specific Regulatory T cells in harnessing cerebral Aβ clearance in Alzheimer’s Disease
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-04-01 → 2020-09-27
- EU contribution
- €187,866
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
Role of Aβ Specific Regulatory T cells in harnessing cerebral Aβ clearance in Alzheimer’s Disease
With populations rapidly ageing, maintaining brain health has become a global priority. The number of people living with dementia is expected to rise to 152 million worldwide within the next 20 years, with an estimated cost upwards of US$1 trillion for dementia care. Clinical trials for vaccination against Aβ, the pathogenic agent accumulating in the brain and triggering Alzheimer’s disease (AD), have failed or worst were accompanied by severe side effects due to an improper response of the immune system. In other neurodegenerative disorders, strategies based on strengthening a population of immune cells from the adaptive immunity named regulatory T cells (Treg) have proven successful. Indeed, Treg have the ability to prevent overly exuberant activation of other immune cells and at the same time direct them toward clearance of pathogens. Using a mouse model of AD, which like patients present Aβ buildup in the brain, the goal of this project was to test a new type of vaccination in hopes that it will activate Treg specifically targeting the Aβ peptide. The objectives are: 1) to assess if Aβ specific Treg produced by the vaccination would prevent improper brain inflammation and control partner immune cells to clear Aβ deposition; 2) To determine if the Treg infiltrate the brain to exert the predicted beneficial effects; 3) To identify other immune cell populations involved in the response to cerebral Aβ deposition.
Data: CORDIS, © European Union
Project objective
With populations ageing, Alzheimer’s disease (AD), for which there is still no cure, has become a major public health problem in Europe. This is partly due to the neglect of the role of the immune responses to the build-up of cerebral Aβ-the pathogenic agent triggering AD. Clinical trials for vaccines aimed at reducing cerebral Aβ were accompanied by severe side effects due to improper neuroinflammation. While the input of microglia, the brain resident innate immune sentinels, is becoming clearer, the impact of the adaptive immune system, specifically T cells is still unknown. A promising therapeutic strategy, would be to strengthen Aβ-induced regulatory T cells (Treg), to alter the effector T cell mediated inflammatory response, while promoting clearance of Aβ by microglia. My interdisciplinary project hosted by Trinity College Dublin and supervised by Prof Lynch will draw together both Neuroscience and Immunology. I propose to assess the effect of Aβ-specific Treg on the pathoethiology of AD. To this aim, I will amplify a population of Aβ-specific Treg in the APP/PS1 mouse model of AD and will 1) assess if Aβ-specific Treg can regulate instruction of microglia to clear cerebral Aβ, while keeping inflammation under control, 2) determine if this regulatory effect occurs via paracrine mechanisms from the periphery or if Treg physically enter the CNS and 3) identify other Aβ-specific T cell populations involved in response to cerebral Aβ build-up and in alteration of microglial phagocytic activity. Completion of this project will make a critical contribution to the understanding of the immune response in AD and will pave the way towards safer therapeutic tools. The proposed action will allow the dissemination of my work to both neuroscientists, immunologists, and the general public. I will reinforce my multidisciplinary and inter-sectoral skills, improve my management and teaching experience to establish myself among the leaders of research at ERC level.
Original text from CORDIS.
Participants
- THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN · DublinCoordinatorIreland
Links
Data: CORDIS, © European Union