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Previously unknown immune cell type is significantly involved in autoimmune diseases such as multiple sclerosis in the brain / Hope for more specific therapeutic approaches with few side effects / Study published in the journal Science

A team of researchers led by the University Medical Center Freiburg has demonstrated in an animal model that previously unknown immune cell types can be found in the inflamed brain during the course of multiple sclerosis (MS). The proof was obtained using a new, high-resolution method for examining individual cells. This enabled the researchers from Freiburg and Munich to create a kind of immune cell atlas for the brain. They also showed how these cells drive the autoimmune disease MS. The researchers present their study in the January issue of the renowned journal Science, which will be published on January 25, 2019.

"Our results represent a breakthrough in the understanding of autoimmune diseases such as multiple sclerosis. We hope that new, more cell-specific therapeutic approaches with fewer side effects can now be developed to treat inflammatory diseases such as MS," says project leader Prof. Dr. Marco Prinz, Medical Director of the Institute of Neuropathology at the Freiburg University Medical Center. "The main problem with the previously inadequate therapy was that the entire immune system was inhibited. However, we were able to find new subtypes of cells that are specific for local inflammation and destruction in MS. These could therefore be specifically switched off," says Prof. Prinz.

Women in particular suffer from multiple sclerosis

Multiple sclerosis is one of the most common inflammatory diseases of the central nervous system (CNS), which includes the brain and spinal cord. Women are affected more frequently than men, and the disease typically occurs for the first time between the ages of 20 and 40. In Germany, around 120,000 people suffer from MS. "MS is thought to be an autoimmune disease in which immune cells mistakenly attack structures of the central nervous system, causing inflammation," explains Prof. Prinz, who is also involved in the Centre for Biological Signalling Studies - BIOSS and Centre for Integrative Biological Signalling Studies - CIBSS clusters of excellence at the University of Freiburg. It has been known for many years that scavenger cells of the blood and brain are involved in MS; however, it was previously unclear exactly which subtypes were involved. In the animal model of multiple sclerosis, scientists have discovered this after years of research.

White spots filled in the immune cell atlas

By using the latest, high-resolution single-cell methods, the researchers have succeeded in deciphering the complex composition of the cells present at the site of inflammation, the so-called inflammatory infiltrate. This enabled them to establish a new immune cell atlas of the brain. The single cell analyses used by the researchers are novel and can be used in medicine to examine individual cells from tissues. In the eyes of the researchers, they have enormous potential. "These methods allow us to obtain a completely new cellular picture of very complex tissues such as the brain," says Dr. Dominic Grün, one of the pioneers of this technique and research group leader at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, who was involved in this study.

The first author of the study, Marta Joana Costa Jordão, a doctoral student at the Institute of Neuropathology at the Freiburg University Medical Center, was also able to show that various phagocytes in the brain remain chronically activated during the disease. Until now, it was assumed that they are rapidly renewed by circulating blood cells. "This permanent activation of immune cells could explain why the brain is chronically attacked over years in MS," says Costa Jordão.

Caption 1: Immunofluorescence of inflammatory changes in the spinal cord with red microglial cells and green macrophages that have migrated from the blood.

Caption 2+3:Comprehensive map of immune cell populations during inflammation in the central nervous system. Each immune cell is a dot, dashed lines include similar cells.

Image source: University Medical Center Freiburg

Original title of the study: Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation

DOI: 10.1126/science.aat7554

Link to the study: science.sciencemag.org/content/363/6425/eaat7554

Contact: 
Prof. Dr. Marco Prinz 
Medical Director 
Institute of Neuropathology 
University Medical Center Freiburg 
Phone: 0761 270-51060 
marco.prinz@uniklinik-freiburg.de