Translational Immunology
We are studying the adaptive immune system to understand B and T cell biology in health and disease. We are epecially interested in immune repertoires.
1 \ B cells in autoimmune liver disease
Autoimmune hepatitis (AIH) is historically considered a T cell-mediated disease. However, the observation that AIH patients have high serum levels of immunoglobulin G (IgG) and circulating autoantibodies also suggests pathological regulation by B lymphocytes which is corroborated by the presence of liver infiltrating plasma cells.
As part of the SFB841, we want to understand the role of B cells in AIH in more detail and investigate to what extent B lymphocytes lead to liver damage via modulation of T lymphocytes.
References
Lübbering et al 2023, Immunology
Schultheiß, Steinmann et al 2023, Hepatol Commun
Schultheiß et al 2022, Semin Immunopathol
2 \ Autoreactive B and T cells
Lymphocytes are indispensable for human health, but can turn “rogue” leading to not only autoimmunity, but also malignant lymphoproliferations. With this project, we aim to lay the foundation of a new common pathobiological understanding of lymphoma and autoimmune diseases. This will hopefully allow us to design and develop a novel type of antigen receptor antagonism for precision targeting of lymphocytes to deliver on the promise of personalized medicine at this crossroad of diseases.
References
Lübbering et al 2023, Immunology
Schultheiß et al 2021, iScience
Simnica et al 2019, Front Immunol
3 \ Understanding early lymphoma development
Since the vast majority of lymphoma data derives from established lymphomas, it remains hypothetical how deregulation of the antigen receptor signaling axis, microenvironmental and inflammatory stimuli as well as the various illegitimate genomic mutational events are sequenced and synergize with each other especially in the protracted pre-malignant phases of positive clonal selection that remain clinically unrecognized. Biological dissection of the very early steps of lymphomagenesis could impact on innovative programs of early detection, early treatment and even prevention.
4 \ Clinical consequences of immune repertoire metrics in age and cancer
The dynamics of immunoaging and the onset of immunoparesis in healthy individuals and cancer patients has been controversially discussed. We have set up a home-brew next-generation immunosequencing pipeline allowing the rapid analysis of hundreds of B and T cell receptor repertoires from mice and man in health and disease. We have used this valuable ressource to study age-dependend effects on immune repertoire metrics, but also linked these to adverse reaction patterns in infectious diseases such as COVID-19. The quest for the holy grail of repertoire metrics predicting response to immunotherapies and other systemic treatments has inspired the translational research programs of many of our clinical trials.
References
Paschold, Gottschick et al 2023, Sci Rep
Ellingsen et al 2022, J. Translational Medicine
van Wilpe et al 2022, Oncoimmunology
Paschold, Simnica et al 2021, JCI
Simnica et al 2020, JCO Precis Oncol
Let's Work Together
Exchange of knowledge is essential for scientific progress. If you have an idea on how we could help you with your project or vice versa just contact us. We are always interested in cooperations.