Prevention, Aging und Systems Immunology

Description

Ageing processes of the immune system The group's research focuses on the role of the immune system in ageing processes and the role the immune system plays in the early stages of chronic inflammatory diseases, particularly in old age. Such inflammatory processes are also increasingly being attributed to the early stages of neurodegenerative diseases. A particular focus is on the ageing processes of the immune system itself, which may exert a decisive influence on the development of inflammatory processes and as a consequence of age-related diseases. Research with state-of-the-art methods for humans The group investigates these processes in cohort studies using the latest methods of immunology, functional genomics and computer-aided analysis of high-dimensional data sets with the aid of statistical and bioinformatic methods, including machine learning and the use of artificial intelligence. Precision medicine requires the development of companion diagnostics (CDx) for the identification of patients benefiting from treatment. Using corticosteroid therapy in ICU patients with severe infection as an example, they have conceptualised a blueprint for CDx development by applying single-cell and bulk transcriptomics to identify molecular characteristics of individuals and monitor drug target engagement. In their latest study, the group demonstrates the potential of single-cell omics for monitoring in vivo target engagement of immunomodulatory drugs and for patient stratification for precision medicine approaches. Dexamethasone-induced transcriptional changes in monocytes are molecular treatment responses directly linked to clinical outcome of severe COVID-19 and highlight the potential for identifying non-responders refractory to dexamethasone. Infections as a trigger for premature ageing of the immune system Another focus is the investigation of infectious diseases as possible triggers for chronic inflammatory processes and premature ageing of the immune system and thus possibly as one of the causes of the development of age-related diseases - including neurodegenerative diseases. In this context, the group is working on the characterisation of the immune response in people living with HIV infection \[HIV2000], people suffering from severe sepsis \[ImmunoSEP], people with acute COVID-19 \[DeCOI], but also post-COVID syndrome \[NEUROCOV, NKSG] and fatigue after viral infections \[IMMME]. These immunological stress situations could lead to long-term damage and premature ageing of the immune system. Improvement of the immune system to prevent ageing processes As part of these cohort studies, the group is also conducting intervention studies. They are investigating how vaccinations work in old age, how they can be optimized, for example in patients with chronic diseases, how already approved drugs can be used to improve the function of the immune system in older people, and how methods of functional genomics can be used to develop diagnostic tests for drug monitoring or as companion diagnostics. Description adapted from working group website: see link above. ​