New LIH review explores how the metabolism of the immune system could unlock better treatments for autoimmune diseases

Researchers identify reactive species as a crucial link between metabolism, immune function, and diseases such as multiple sclerosis, rheumatoid arthritis and lupus.

• Experimental and Molecular Immunology
• Department of Infection and Immunity

In a new review published in the journal Cell Metabolism, authors Dr Takumi Kobayashi and Prof. Dirk Brenner from the Experimental & Molecular Immunology Group at the Luxembourg Institute of Health (LIH) show that tiny reactive molecules inside cells play a much more important role in autoimmune diseases than previously thought.

Reactive oxygen and nitrogen, collectively known as reactive species, are usually portrayed as harmful molecules that damage cells, hence the popularity of antioxidants in consumer goods. However, the research shows that they also play an essential role in healthy immune function. When produced in carefully controlled amounts in specific locations, they act as chemical messengers that help immune cells communicate, respond to infection, and regulate energy usage.

When this balance is disrupted, however, the immune system tends to malfunction. Damage caused by the accumulation of reactive species can trigger chronic inflammation and cause immune cells to attack healthy tissue, contributing to autoimmune disease.

Rather than looking at these processes in isolation, the authors collected evidence from across the field to show how metabolism, reactive species, and immune function are closely interconnected. They argue that understanding these links could help researchers develop more precise treatments that restore healthy immune function instead of broadly suppressing the entire system.

“Reactive species are often seen as something we need to eliminate, but biology is not that straightforward. In fact, we need these molecules for a healthy immune response. The challenge is to understand when, where, and in which cells they become harmful. That knowledge will help us design smarter therapies that target disease more precisely while preserving the normal functions of the immune system,” said Prof. Dirk Brenner, Head of the Experimental & Molecular Immunology Group at the LIH.

The review also explains why many antioxidant-based therapies have shown limited success in patients. Instead of reducing reactive species throughout the entire body, the authors suggest that future treatments should restore their balance in the specific immune cells driving disease. To that end, several promising approaches are already emerging, including therapies that target mitochondria, regulate ferroptosis (an iron-dependent form of regulated cell death), and engineer immune cells.

Clinically the findings are particularly relevant to CLINNOVA, a pan-European precision medicine initiative coordinated by the LIH, which focuses on the diseases mentioned in the review, namely rheumatoid disease, inflammatory bowel disease, and multiple sclerosis. A better understanding of the biological mechanisms behind these diseases could improve biomarker discovery and help identify the most effective treatment for each patient.