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Cross-talk between platelets and immunity - implications for host homeostasis and defense

Description du projet

Aperçu mécanistique de l’immunothrombose

La reconnaissance des agents pathogènes par des cellules spécifiques du système immunitaire telles que les monocytes et les neutrophiles active également le système de coagulation. Cette coopération, connue sous le nom d’immunothrombose, permet le piégeage des agents pathogènes, limitant leur propagation dans le compartiment vasculaire et empêchant la lésion d’autres organes. Le projet IMMUNOTHROMBOSIS, financé par l’UE, a pour objectif de disséquer le mécanisme à l’origine de ce phénomène et de comprendre comment il pourrait être impliqué dans les maladies cardiovasculaires. Les chercheurs porteront leur attention sur les plaquettes et révéleront leur rôle dans la synergie homéostatique et pathogène de la thrombose et de l’inflammation. Les résultats ouvriront la voie à de nouvelles interventions contre la formation de thrombi et les maladies cardiovasculaires.  

Objectif

The overall aim of the IMMUNOTHROMBOSIS project is to clarify the mechanisms underlying the recently identified synergism between thrombosis and inflammation. Thrombus formation and inflammation are vital host responses that ensure homeostasis, but can also drive cardiovascular disease, including myocardial infarction and stroke, the major causes of death in Europe. My group and others discovered, that thrombosis and inflammation are not to be considered separate processes. They are tightly interrelated and synergize in immune defence, but also in inflammatory and thrombotic diseases in a process we termed immunothrombosis. Targeting this synergism has great potential to identify innovative and unconventional strategies to more specifically prevent undesired activation of thrombotic and inflammatory pathways. However, this requires a deeper mechanistic understanding of immunothrombosis. I recently identified two ground-breaking novel immunothrombotic principles: I discovered that platelets have the ability to migrate autonomously, which assists immune cells in fighting pathogens. Further, I revealed that immune cells play a central role in controlling the production of platelets from their megakaryocyte precursors. The physiological and pathophysiological relevance of both processes is unclear. This is the starting point and focus of the IMMUNOTHROMBOSIS project. My aim is to define how platelets use their ability to migrate to support immune cells in protection of vascular integrity (objective 1) and to identify the contribution of platelet migration to different cardiovascular diseases involving immunothrombotic tissue damage (objective 2). Finally, I will clarify how inflammatory responses feedback to the production of thrombotic effectors and dissect inflammatory mechanisms that control platelet production (objective 3). IMMUNOTHROMBOSIS will identify new options for specific prevention or treatment of thrombotic and inflammatory cardiovascular diseases.

Régime de financement

ERC-ADG - Advanced Grant

Institution d’accueil

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Contribution nette de l'UE
€ 2 321 416,00
Adresse
GESCHWISTER SCHOLL PLATZ 1
80539 MUNCHEN
Allemagne

Voir sur la carte

Région
Bayern Oberbayern München, Kreisfreie Stadt
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 2 321 416,00

Bénéficiaires (1)