The role of harmful immune cells in multiple sclerosis

Researchers at the University of Zurich have identified T-helper cells that move from the blood to the central nervous system, where they cause inflammation and damage the nerve cells. Their discovery opens up new possibilities for monitoring and treating MS.

A new study discovers a suspicious cell group

Researchers at the University of Zurich have identified defense cells that are likely to play a key role in multiple sclerosis (MS). T-helper cells move from the blood to the central nervous system, where they cause inflammation and damage the nerve cells. Their discovery opens up new possibilities for monitoring and treating MS.

"Fingerprints" of harmful immune cells detected

MS research has been searching for years for the "fingerprints" of the immune cells that are characteristic of this disease. This is exactly what an international team led by Burkhard Becher at the Institute for Experimental Immunology at the University of Zurich (UZH) has achieved. "In MS patients’ blood, we have identified a specific population of white blood cells that have two abilities characteristic of MS: They can escape from the blood into the central nervous system (CNS) and lead to inflammation of the nerve cells," explains Becher.

State-of-the-art cell measurement and artificial intelligence

For their search, the team used a technology to characterize immune cells: large scale cytometry. This makes it possible to examine millions of cells in hundreds of individuals and determine their immune characteristics - the "fingerprints". The scientists developed new computer algorithms to be able to analyze the huge amounts of data. "Thanks to artificial intelligence and machine learning, data complexity can be enormously reduced, while the interpretation of the results is left to the researchers," said Burkhard Becher.

Key characteristics of misdirected immune cells

The interdisciplinary team consisting of physicians, biologists and computer scientists succeeded in identifying a cell population in the peripheral blood of MS patients that clearly differs from the defense cells from blood samples taken from people with other inflammatory and non-inflammatory diseases. These misdirected T-helper cells produce the neuroinflammatory cytokine GM-CSF. On the other hand, these immune cells contain large amounts of the chemokine receptor CXCR4 and the membrane protein VLA4.

"The now identified cell population thus has central MS-typical properties: The cytokine triggers neuronal inflammations and, thanks to the receptors, the immune cells can penetrate the CNS," says Edoardo Galli, first author of the study. The researchers also found that the defense cells that are characteristic of MS are also strongly represented in the brain fluid and in the patients’ brain damage. This suggests that they have a direct influence on the disease. In addition, therapy greatly reduces this population.

Strong evidence, but no settled proof

"Our results clearly indicate a direct link between the MS immune characteristics and the disease. The biomarker we identified should be very useful for the monitoring of MS patients," explained Burkhard Becher. Despite the strong evidence, it is still too early to claim that the specific T-cell population causes the disease. As a first step, further studies are needed to confirm the hypothesis. If the suspicion is confirmed, the detailed characterization of these immune cells will probably also lead to new therapies.

Edoardo Galli, Felix J. Hartmann, Bettina Schreiner, Florian Ingelfinger, Eirini Arvaniti, Martin Diebold, Dunja Mrdjen, Franziska van der Meer, Carsten Krieg, Faiez Al Nimer, Nicholas Sanderson, Christine Stadelmann, Mohsen Khademi, Fredrik Piehl, Manfred Claassen, Tobias Derfuss, Tomas Olsson & Burkhard Becher. GM-CSF and CXCR4 Define a T Helper Cell Signature in Multiple Sclerosis. Nature Medicine. July 22, 2019. DOI: 10,1038/s41591-019-0521-4

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