TRR 332 – Neutrophil Granulocytes: Development, Behaviour & Function

Rheumatoid arthritis is one of the most common autoimmune diseases. The chronic joint inflammation occurs when the body’s own immune cells attack the tissue. The mechanisms that trigger this autoimmune disease are not yet fully understood. Researchers in the special research division Transregio 332 »Neutrophil granulocytes: development, behaviour & function« want to change this. The purpose of their work is to provide important insights into the mechanisms of neutrophil granulocytes, and eventually help provide patients with rheumatoid arthritis better treatment in future.

At ISAS, scientists in the subproject »Phagocytic crosstalk between neutrophils and macrophages« investigate how immune cells of the type of phagocytes – in specific neutrophil granulocytes and macrophages – communicate with one another. They also analyse the effect of this communication on the disease process. Their aim: To identify and characterise various functional subtypes of neutrophils that induce the joint inflammation that accompanies rheumatoid arthritis and play a part in ensuring that the disease becomes chronic.

Regulation of neutrophil subtypes for new treatment approaches

Neutrophil granulocytes are known to play a key role in the pathogenesis of rheumatoid arthritis. It has also been assumed for a long time that these cells represent a uniform population with uniform functions. Recent research however has revealed that different subgroups exist – independently of the rheumatoid arthritis – and that they can perform different functions. With their subproject researchers at ISAS and the University of Münster have already demonstrated in the case of rheumatoid arthritis that various subgroups of neutrophils infiltrate different areas of the joint.

The scientists research the functions these subgroups perform in the respective tissue niches and their effect on the development of the disease using multimodal imaging methods including light sheet fluorescence microscopy and confocal microscopy. Flow cytometry and spatial transcriptomics analyses are also used in this case. Establishing the latter sequencing analysis on bone tissue is a methodical challenge, as up until now a standardised protocol for this does not exist anywhere in the world. The project team investigates the neutrophil granulocytes in mouse models and also in human samples. The knowledge acquired should in the long term lead to new treatment approaches based on a regulation of the neutrophil subtypes.