CD Laboratory for Immunometabolism and Systems Biology of Obesity Related Disease (InSpiReD)

The immune system reacts differently in healthy and sick people, as immune cells can be reprogrammed by obesity, for example. These processes and changes are being researched here in order to identify therapeutic target structures.

Blood fats (lipids) and metabolic products (metabolites) play an important role in the activation, differentiation and functionality of haematopoietic (myeloid) cells, e.g. macrophages. One of the key functions of macrophages is the removal of dying or dead cells. This process is called efferocytosis, which, derived from the Latin efferre, roughly means "burying dead cells".

During efferocytosis, dead cells are completely surrounded and removed by the macrophages before their membrane integrity is damaged and their partially toxic contents are released into the surrounding tissue. In addition to myeloid macrophages, there are also tissue-specific macrophages. For example, these promote vascularisation in fatty tissue, remove dying fat cells and influence the remodelling and formation of fatty tissue.

The functioning of macrophages can be changed and reprogrammed by their respective microenvironment even after they have matured. The microenvironment also includes the substances that are released by efferocytosis, i.e. lipids and metabolites. Such reprogramming also affects the efficiency of efferocytosis itself and defective efferocytosis in turn is associated with various diseases.

This CD Laboratory investigates the influence of different forms of cell death and, in particular, secreted lipids and metabolites on the position of macrophages. The aim is to identify features that are common to different signalling pathways in immune cells and pathological processes. For example, the immunometabolic properties of macrophages during efferocytosis will be compared with those of macrophages that are heavily loaded with lipids due to obesity.

The investigations will be carried out on preclinical models of obese liver fibrosis and cancer as well as in patient cohorts. By analysing lipid and metabolite levels in blood and tissue samples and profiling immunophenotypes, it will be possible to identify signalling pathways and therapeutic targets that are altered in inflammatory diseases and cancer. The aim is to research the basis for the development of new immunotherapies that will ultimately benefit human health.