(Vienna, 19 May 2026) Multiple sclerosis (MS) is a chronic condition in which the immune system attacks the central nervous system. In this process, immune cells migrate into the brain and spinal cord and trigger inflammation. The role played by metabolic processes in this process has not yet been fully elucidated. An international research team led by MedUni Vienna has now identified a key mechanism: invading immune cells specifically alter metabolism in the inflamed nervous tissue – thereby influencing the course of the disease. The findings, currently published in the leading journal Nature Immunology, may contribute to the development of new therapeutic approaches in the long term.
The research team led by lead authors Martina Kerndl, Laszlo Musiejovsky, Andrea Komljenovic and Hon Shing Lam (all from the Center for Physiology and Pharmacology at MedUni Vienna) focused their investigations on the amino acid arginine. The researchers were able to show that certain immune cells in the inflamed tissue produce increased levels of an enzyme called arginase-1, which breaks down arginine. The resulting local arginine deficiency has various consequences: the immune cells become "stressed", their lipid metabolism is thrown out of balance and anti-inflammatory processes are weakened.
"We were able to show that immune cells that have migrated into the central nervous system specifically break down arginine and thereby influence the course of the disease," explains co-study leader Omar Sharif (Center for Physiology and Pharmacology and Christian Doppler laboratory for Immunometabolism and Systems Biology of Obesity-related Diseases, MedUni Vienna). Monocytes play a central role here – immune cells that enter the nervous system from the blood and continue to develop there: "We have identified these cells as the most important source of arginase-1; they significantly shape the inflammatory environment in the central nervous system," explains co-first author Laszlo Musiejovsky. The researchers also found similar cells in tissue samples from MS patients.
Experiments in a mouse model also show that if less arginine is available, the disease worsens. If, however, arginase-1 is specifically knocked out in these cells, the disease takes a significantly milder course." Our findings suggest that arginine plays a protective role in inflamed nervous tissue," says co-study leader Gernot Schabbauer (Center for Physiology and Pharmacology and Christian Doppler laboratory for Arginine Metabolism in Rheumatoid Arthritis and Multiple sclerosis, MedUni Vienna). At the same time, the researchers emphasise that arginine metabolism differs between mice and humans. Further studies will now seek to clarify exactly how arginine influences inflammatory processes and lipid metabolism in immune cells, and what role these mechanisms play in humans.
Multiple sclerosis is one of the most common chronic inflammatory diseases of the central nervous system and affects millions of people worldwide. Symptoms range from visual disturbances and mobility problems to severe fatigue. The disease often progresses in relapses and is currently incurable. Available therapies aim to influence the immune system and reduce disease activity. The new findings on the interaction between immune cells and metabolism could, in the long term, contribute to the development of new therapeutic strategies.
Publication: Nature Immunology
Monocyte infiltration induces CNS arginine catabolism to fuel neuroinflammation.
Martina Kerndl#, Laszlo Musiejovsky#, Andrea Komljenovic#, Hon Shing Lam#, Andrea Vogel, Tobias Bausbacher, Christian J. Riedl, Roko Sango, Lenka Matejovicova, Anja Dobrijevic, Laura Oberbichler, Melanie Hofmann, Markus Kieler, Lucia Quemada Garrido, Lara Veronika Perko Budja, Julia Stefanie Brunner, James Lucas Cairns, Paul Cheng, Kerstin Kitt, Christine Isaguirre, Thomas Köcher, Kristaps Klavins, Thomas Rattei, Simon Hametner, Stephan Blüml, Carsten Hopf, Ryan D. Sheldon, Omar Sharif* & Gernot Schabbauer*.
DOI: 10.1038/s41590-026-02516-4
https://www.nature.com/articles/s41590-026-02516-4