Project description
Research uncovers platelet role in inflammation and immune response
Platelets, known for their role in stopping bleeding (haemostasis) and forming clots (thrombosis), are now increasingly recognised as key regulators of immune responses and inflammation. They influence immune cell trafficking and endothelial barrier function and protect organ integrity, but they can also lead to organ damage in conditions like stroke and sepsis. A groundbreaking discovery reveals that platelets can reorganise their main adhesion receptor along with a signalling machinery into so-called disintegration complexes, which form a new organelle known as ‘platelet-derived integrin and tetraspanin-enriched tether’ (PITT). These PITTs, packed with immune-modulatory proteins and RNA, can provoke thrombo-inflammation. The ERC-funded PITT-Inflame project aims to explore these mechanisms and develop new therapies. Understanding this process may transform how various diseases are treated.
Objective
Platelets are mediators of haemostasis and thrombosis, but also increasingly recognized as versatile effector cells of innate immunity. The concept of thrombo-inflammation recognizes that thrombotic and inflammatory pathomechanisms are closely intertwined. Platelets thereby act as central orchestrators of immune cell trafficking, vascular barrier function and organ integrity and contribute to organ injury in severe disorders with limited treatment options (e.g. stroke, sepsis, ARDS). The underlying molecular mechanisms are not known.
I recently discovered an unexpected novel effector mechanism in platelets with potentially huge impact for understanding these cells in health and disease: Resting platelets can rapidly reorganize the entire pool of their principal adhesion receptor, integrin IIb3, along with its associated tetraspanins and signalling machinery into disintegration complexes (DISCs) in distinct membrane microdomains. These DISCS serve as building blocks for a novel organelle, the Platelet-derived Integrin and Tetraspanin-enriched Tether (PITT). PITTs are loaded with signalling molecules, ribosomes and RNA and can segregate from the platelet to promote thrombo-inflammation. Also 1-integrins as well as glycoprotein (GP)VI can be integrated into DISCs and deposited at discrete adhesion points.
I therefore postulate that circulating platelets have the capacity to use their principal adhesion/signalling machineries in two fundamentally different ways and thereby switch between the haemostatic and a thrombo-inflammatory effector programme. If proven correct, this would implicate a radically new paradigm in platelet biology, and open new avenues for the treatment of a wide range of diseases with major societal impact.
PITT-Inflame will (i) provide a detailed molecular composition and architecture of DISCs and PITTs; (ii) decipher underlying signalling networks; (iii) identify PITT-induced effects on target cells and (iv) deduce therapeutic strategies.
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.
- medical and health sciences clinical medicine angiology vascular diseases
- medical and health sciences basic medicine neurology stroke
- 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)
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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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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.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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(opens in new window) ERC-2023-ADG
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97080 WURZBURG
Germany
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