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Quantification of leukocyte chemoattractants to identify specific drug targets for chronic rejection in lung transplantation

Neutrophils are the most abundant leukocytes in the human blood circulation and mediate a fast immune response to infection and tissue damage. Directional leukocyte migration throughout the body is meticulously regulated by chemokines, which are small and structurally conserved chemotactic proteins. Notably, chemokine activity is spatiotemporally controlled at multiple levels, including through post-translational modifications such as proteolysis. Resulting chemokine proteoforms can display a significantly altered biological activity compared to the intact proteins. Excessive neutrophil activation may result in collateral tissue damage during uncontrolled inflammation. In patients with severe coronavirus disease 2019 (COVID-19) or chronic lung allograft dysfunction (CLAD) following lung transplantation, neutrophils, proteases and chemokines are associated with disease severity and pathogenesis. Therefore, the objective of this PhD project is to characterize neutrophils and investigate chemokine proteolysis in the blood and broncho-alveolar lavage (BAL) fluids of COVID-19 and CLAD patients. As such, we aim to improve our understanding of neutrophil phenotypical and functional heterogeneity and their contribution to the pathogenesis of these diseases. Moreover, we aim to identify novel drug targets that could be exploited to reduce excessive neutrophil recruitment and inflammation.

Date:1 Oct 2019 →  28 Nov 2023
Keywords:Chemokines, Chronic rejection, Lung transplantation, Neutrophils, COVID-19, Proteolysis
Disciplines:Inflammation, Transplantation immunology, Proteins, Innate immunity, Infectious diseases, Posttranslational modifications
Project type:PhD project