Project description
Molecular mechanisms of mucosal immunity
Mucosal surfaces throughout the body, such as in the linings of the gastrointestinal and respiratory tracts are the primary points of contact with the external environment. Mucosal immunity plays a central role in protecting against infection but also preventing inflammatory responses. Funded by the European Research Council, the GREMLIN project is interested in delineating the molecular pathways that govern mucosal-associated lymphoid tissues (MALTs), specialised immune structures in mucosal surfaces. Researchers will explore the role of G protein-coupled receptors (GPCRs) on the recruitment and positioning of immune cells within MALTs during inflammation. Project findings have the potential to determine GPCRs as therapeutic targets for clinical interventions.
Objective
Mucosal immunity is essential to preserve homeostasis and for pathogen control within the gut and the airways. The emerging dogma of immune regionalization has opened to new questions about which elements drive cell adaptation to different niches, and how this can be targeted to cure diseases. The intestine and the airways are functionally diverse along their length, and disorders can differentially impact on different mucosal tissue regions. Mucosa-associated lymphoid tissues (MALTs) are located along the intestine and the airways to drain selective tissue segments and support protective immunity. Whether MALTs located in different tissue areas show immune regionalization remains poorly understood. Also, little is known about which molecules control such immune diversity. G protein-coupled receptors (GPCRs) are surface proteins important for cell migration and compartmentalization in lymphoid tissues, but their role in immune regionalization is not clear. We propose to apply a combination of imaging, flow cytometry, spatial gene editing and sequencing techniques to study the role of GPCRs in immune regionalization of MALTs, at steady state and in disease. In the intestine, we will phenotypically and functionally profile immune cells and GPCRs expression within Peyer's patches (PPs) from different gut regions, in physiology or in the context of inflammation and obesity. Similarly, we will analyze immune regionalization of bronchus-associated lymphoid tissues and nose-associated lymphoid tissues within the airways, at steady state or upon infections. Finally, we will characterize the role of a candidate GPCR, GPR35, in the induction of intestinal and respiratory immunity. Our preliminary data show that GPR35 shapes cell recruitment to inflamed airways and influences cell positioning within PPs. By applying the above-mentioned approaches and dedicated mouse models, we will study how GPR35 regulates mucosal immunity and if it represents an attractive clinical target.
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 physiology homeostasis
- medical and health sciences health sciences nutrition obesity
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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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HORIZON.1.1 - European Research Council (ERC)
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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.
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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.
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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-2023-STG
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20132 Milano
Italy
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