How Itaconate Travels Through Space and Time to Shape Our Immune Response Scientists from Braunschweig and San Diego track the path of the small molecule itaconate to understand its immunomodulatory function

Itaconate is a small molecule produced in our bodies to fight bacteria and modulate immune responses. However, how itaconate travels through the body is not well understood. To close this gap, an international team of scientists led by Thekla Cordes, Professor of Cell Metabolism at Technische Universität Braunschweig at the Braunschweig Centre for Systems Biology (BRICS) and Helmholtz Centre for Infection Research (HZI), together with Professor Christian Metallo at the Salk Institute for Biological Studies in San Diego (USA) and researchers from the University of California, San Diego (USA), uncovered how itaconate moves through space and time within the body to shape our immune responses. These findings open new avenues for potential treatments of inflammatory diseases.

The study, published September 10 2025 in Nature Metabolism, adds to the growing interest in itaconate and provides a novel perspective on its role in regulating metabolism.

t cells produce high amounts of itaconate to alter immune responses, and we were interested in whether cells recycle it to fuel metabolic processes,” says Professor Cordes. To track where itaconate travels in the body and how cells break it down, the interdisciplinary team used specially labeled itaconate. “Our tracing approach is similar to putting a GPS tracker on a car to follow its journey. We use non-toxic stable isotopic tracer technology combined with mass spectrometry methods to track molecules like itaconate within the complex metabolic pathways of living organisms,” explains Hanna Willenbockel, a member of the Cordes research team and first author of the study.

Using this technology, the team discovered that most itaconate is rapidly filtered out of circulation through the kidneys. Some itaconate is converted into key metabolic intermediates such as acetyl-CoA and mesaconate, and it also becomes part of the citric acid cycle in mitochondria. Additionally, it is transformed into a compound called itaconyl-coenzyme A, which influences enzymes involved in energy production and amino acid processing.

The research team has demonstrated in previous studies that itaconate reversibly inhibits the enzyme succinate dehydrogenase that reduces cellular damage associated with reoxygenation. “Our pharmacokinetic studies with itaconate highlight how it dynamically regulates succinate dehydrogenase and other key enzymes as well as overall metabolic processes. Scientists are looking into how itaconate could be used to treat diseases, and our findings might help create better treatments in the future,” says Cordes.

However, the researchers caution that it is premature to take itaconate supplements to influence immune responses and that further studies are needed which may take several years.

Based on: “Willenbockel, H.F., Williams, A.T., Lucas, A. et al. In vivo itaconate tracing reveals degradation pathway and turnover kinetics. Nat Metab (2025). https://doi.org/10.1038/s42255-025-01363-1: https://www.nature.com/articles/s42255-025-01363-1.