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

Descripción del proyecto

Nuevos conocimientos mecanicistas sobre la inmunotrombosis

El reconocimiento de agentes patógenos por células específicas del sistema inmunitario, como los monocitos y los neutrófilos, también activa el sistema de coagulación. Esta cooperación, conocida como inmunotrombosis, conduce al atrapamiento de agentes patógenos, lo que limita su propagación al espacio vascular y previene la lesión de otros órganos. El proyecto IMMUNOTHROMBOSIS, financiado con fondos europeos, tiene por objeto determinar el mecanismo subyacente a este fenómeno y comprender cómo puede estar implicado en las enfermedades cardiovasculares. Sus investigadores se centrarán en las plaquetas y desvelarán su función en la sinergia homeostática y patógena de la trombosis y la inflamación. Los resultados posibilitarán el desarrollo de nuevos tratamientos contra la formación de trombos y las enfermedades cardiovasculares.  

Objetivo

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.

Régimen de financiación

ERC-ADG - Advanced Grant

Institución de acogida

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Aportación neta de la UEn
€ 2 321 416,00
Dirección
GESCHWISTER SCHOLL PLATZ 1
80539 MUNCHEN
Alemania

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Región
Bayern Oberbayern München, Kreisfreie Stadt
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 2 321 416,00

Beneficiarios (1)