Universitätsmedizin Mannheim

Hypoxia-immune signaling in NK cells during critical illness
Abschluss: Dr. med.
Art: experimentell
Für Studierende der: Medizin
Start: sofort
voraussichtliche Dauer: 12 Monate
ungefährer Arbeitsaufwand: 100%
Abteilung: Anästhesiologie und Operative Intensivmedizin
Doktorvater / -mutter: PD Dr. Holger A. Lindner
Betreuer: Dr. Sonia Y. Velásquez
Ansprechpartner: PD Dr. Holger A. Lindner
Kontakt: holger.lindner@medma.uni-heidelberg.de


Inflammation is associated with development of tissue hypoxia. Failure to resolve inflammatory hypoxia favors immunosuppression as seen in critically ill patients. Inflammatory cytokines initially augment the adaptive hypoxia response in NK cells. We hypothesize that continued hypoxic immune stimulation supports an anti-inflammatory NK cell phenotype. Blood NK cells from critically ill patients with trauma-induced systemic inflammation but not with sepsis are characterized by elevated immune checkpoint protein expression and by impaired immune signaling. The MD project will investigate the contribution of hypoxia-immune signaling interactions to these phenotypic differences in patients admitted to intermediate or intensive care. NK cells from patient blood will be stimulated in vitro and analyzed for immune checkpoints and effector activities by flow cytometry and live cell imaging. We expect this project to provide insight into sepsis pathogenesis towards improved prediction and diagnosis of sepsis in the critically ill.
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