Project description
Colorectal cancer may result from too much of a good thing
Tissue repair is regulated by a complex interplay among the immune system, injured tissue and microbiota. To make matters more complicated, inflammation can play a positive or a negative role. The molecular mechanisms underlying the interactions are largely unknown. Inflammatory bowel disease and colorectal cancer provide an opportunity to investigate the relationships among inflammation, immunity, microbiota, tissue repair and signalling pathways gone awry. The EU-funded project REpAIR is studying interleukin-22 (IL-22) and its inhibitor in these disease processes. IL-22, produced by immune cells, acts on intestinal epithelial cells to modulate microbiota composition and promote tissue regeneration. However, it can also promote chronic inflammation and cancer. Outcomes will shed light on how the same pathways can lead to either a physiological repair response or to disease and point to targeted therapies for immune-related diseases and cancer.
Objective
Inflammation is fundamental to promote tissue regeneration upon injury, and in turn, the resolution of the immune response. Physiological tissue regeneration depends on fine-tuned interaction between the immune system, the tissue, and the microbiota. However, the complex communication between these three components and the molecules that mediate it are unclear. Understanding this is fundamental to prevent immune-mediated diseases and even cancer. This is particularly important at mucosal surfaces, where continued regeneration occurs. Therefore, we hypothesize that inflammatory bowel disease (IBD) and colorectal cancer (CRC) are a consequence of a miscommunication between these components.
Interleukin-22 (IL-22) is one key orchestrator of this communication: It is produced by immune cells and by acting on intestinal epithelial cells, it modulates the composition of the microbiota and promotes tissue regeneration. However, IL-22 can also promote both chronic inflammation and cancer. Exactly what regulates these paradoxical effects remains unclear. Of note, there is an endogenous inhibitor of IL-22, namely IL-22 binding protein (IL-22BP), which blocks IL-22 activity. We hypothesize that a misguided spatio-temporal regulation of the IL-22 – IL-22BP axis is the cause of pathogenic effects of IL-22.
In particular, we will analyse: (i) the location, and the functional and molecular heterogeneity; (ii) the origin and fate of IL-22 and IL-22BP producing immune cells; and (iii) the role of the microbiota in regulating them. To this end, we will use new transgenic and gnotobiotic mouse models, single cell RNA sequencing and human samples.
In short, by studying the IL-22 - IL-22BP axis, we will understand how the complex interactions between the immune system, the tissue, and the microbiota lead to either physiological or pathological tissue regeneration. This will provide the basis for therapies controlling inflammation and tissue regeneration in a spatio-temporal manner.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-COG - Consolidator Grant
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2019-COG
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20251 Hamburg
Germany
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