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Projekt Druckansicht

Die Rolle von Interleukin 3 in der Atherosklerose

Fachliche Zuordnung Kardiologie, Angiologie
Förderung Förderung von 2017 bis 2021
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 398190272
 
Erstellungsjahr 2022

Zusammenfassung der Projektergebnisse

This project evaluates the role of interleukin 3 (IL-3) in atherosclerosis. We hypothesized that IL- 3 accelerates inflammatory leukocyte production in the bone marrow and therefore promotes atherosclerotic plaque growth. Surprisingly, however, atherosclerotic mice that lack IL-3 develop larger plaques compared to control mice. As of today, in depth mechanistic studies involving bone marrow transplantation experiments, flow cytometry, gene expression profiling, and cellspecific knockout models suggest a mechanism, in which IL-3 produced by stromal cells in the plaque acts on plaque macrophages improving their capacity to perform functions such as efferocytosis. The time-consuming development of cell-specific knockout models on atherosclerotic background, involving CRISPR/Cas9 based generation of an entirely new mouse line as well as multiple breeding steps thereafter have significantly advanced this project and will allow us to answer the remaining questions in a timely manner. In the meantime, I developed a second main project that combined my backgrounds in neuroscience, cardiology, and immunology. The purpose of this project was to understand how different brain regions control the immune system under conditions of psychosocial stress. Using state-of-the-art tools of neuromodulation including chemo- and optogenetics alongside with classical immunological techniques, we precisely describe how specific brain regions induce large-scale leukocyte shifts between the bone marrow and peripheral organs within hours of stress exposure. During acute stress, high numbers of neutrophils are released from the bone marrow to prepare the body for potential injuries in fight or flight situations, whereas monocytes and lymphocytes show a mass migration into the bone marrow to potentially prevent the development of autoimmunity during episodes of tissue injury with high levels of free autoantigens. While these large-scale bidirectional leukocyte shifts may be beneficial in fight-orflight situations, we show that they can be detrimental when acute stress coincides with exposure to influenza and SARS-CoV-2. The results have broad implications for our understanding of brain-immune communication and have recently been published in several Nature articles with widespread attention from the scientific community as well as from mainstream media outlets.

Projektbezogene Publikationen (Auswahl)

 
 

Zusatzinformationen

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