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Researchers at the University of Freiburg identify common patterns of immune defense in human brain tissue and in a mouse model / Analyses reveal where immune cells are active in diseases / A foundation for future therapies

Diseases such as Alzheimer’s disease, multiple sclerosis, and brain tumors progress in very different ways. Nevertheless, the human brain’s immune system employs similar response patterns in these conditions. Researchers from the Faculty of Medicine – University of Freiburg, in collaboration with an international team, have now demonstrated this through analyses of human brain tissue and mouse models. They also created detailed maps of the brain showing where specific immune cells appear in diseases. This allows important conclusions to be drawn about their function. The findings improve our understanding of the immune defense in the brain and could help develop more targeted therapies in the long term. The study was published on March 25, 2026, in the journal Nature Immunology.

“Our results show that immune cells in the brain respond according to similar patterns in different diseases. The immune system has a finite set of building blocks and programs that are combined in different ways,” says study leader Prof. Dr. Marco Prinz, Medical Director of the Institute of Neuropathology at the Medical Center – University of Freiburg and a member of the Cluster of Excellence Centre for Integrative Biological Signaling Studies (CIBSS) at the University of Freiburg. These building blocks include, among other things, the protection of nerve cells, inflammatory reactions, cell division, and the activation of other brain cells. “This helps us describe disease-relevant processes more precisely and better identify potential targets for future therapies.”

Microglia perform important functions in the brain

The study focused on microglia. These are immune cells that are permanently present in the brain. They monitor the nervous tissue, remove cell debris, and respond to inflammation, injury, or the death of nerve cells. For the study, the research team examined immune cells from human brain tissue obtained from patients with various diseases of the central nervous system. In addition, the researchers analyzed mouse models using the same experimental and computer-based methods. This allowed them to demonstrate that key patterns of the immune response found in human tissue also occur in mouse models in a similar form.

Not only the type of response, but also its location is important

“It was crucial for us not only to identify which microglial programs exist, but also where they occur in the diseased tissue,” says Dr. Chintan Chhatbar, first author of the study at the Institute of Neuropathology at the Medical Center – University of Freiburg. “Only then does it become clear which reactions are likely directly linked to typical disease processes.” For example, in Alzheimer’s disease, certain microglial activations were found near typical protein deposits; in multiple sclerosis, they tended to be at the edges of lesions; and in brain tumors, they were in the immediate vicinity of tumor cells.

The study expands on earlier research that mapped the distribution of individual cell types in the brain, providing a disease-transcending and spatially resolved classification.

Important foundation for future applications

The results provide an important foundation for better comparing the immune response in the human brain across various diseases and for more precisely identifying potential targets for treatments. In the next steps, the researchers aim to investigate which of these programs can be specifically targeted and what role they might play in the future for diagnostics, monitoring disease progression, and therapy.

Original title of the publication:A transcriptomic microglia taxonomy across mouse and human pathologies
DOI: 10.1038/s41590-026-02472-z
Link to the study: https://doi.org/10.1038/s41590-026-02472-z