Project description
The role of naïve T cells in organ inflammation
Immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and Crohn’s disease, are conditions where the immune system mistakenly attacks the body’s own tissues causing inflammation in specific organs. The incidence of IMIDs is rising, particularly in industrialised countries, but the mechanisms behind their organ specificity and increasing prevalence remain unclear. Exposure to environmental factors like pollution and western diets may contribute to this trend. The working hypothesis of the ERC-funded ADAPT project is that naïve CD4+ T cells may play a critical role in organ-specific IMIDs. Researchers will investigate whether these T cells adapt to specific organs, creating localised immune niches that may be triggered by harmful environmental factors thus initiating IMIDs.
Objective
Organ-specific immune-mediated inflammatory diseases (IMIDs) have a growing socio-economic impact due to their steadily increasing incidence. At least two aspects are still unclear: what immunological mechanisms restrict these diseases to one or a set of specific organs and what triggers the continuously increasing incidence, particularly in industrialized countries. Increasing exposure to harmful environmental triggers, such as pollution but also Western diet, have been suggested as potential reasons. We propose that when locally active immune cells are perturbed by harmful environmental triggers this leads to organ-specific IMIDs.
Naïve CD4+ T cells have so far been considered a quasi-homogenous and inert population excluded from organs. Therefore, their contribution to organ-specific IMIDs has been overlooked. Contrary to this, there is evidence that naïve T cells circulate through organs and diversify into different subpopulations reflecting the organ they patrol.
This project aims to reveal whether organ adaptation of naïve T cells in steady state is one of the key mechanisms contributing to the organization of the immune system into districts of competence - i.e. areas of inflammation. We also aim to understand whether organ-specific naïve T cells responding to harmful environmental triggers set the early premise for the development of organ-specific IMIDs.
We will study this using a unique portfolio of healthy and diseased human organs in combination with multi-modal single-cell technologies to gain an unprecedented resolution in the analysis of naïve T cells. Next, we will use mouse models and 3D human cocultures to test naïve T cell function and response to environmental triggers.
This project will influence the current understanding of how the activity of the immune system is adapted and distributed throughout the body, which will also push the boundary of precision medicine to consider organ-specific naïve T cells when designing future immunotherapies.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health scienceshealth sciencesnutrition
- natural sciencesearth and related environmental sciencesenvironmental sciencespollution
- medical and health sciencesbasic medicineimmunologyimmunotherapy
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Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
20251 Hamburg
Germany