New immune signaling pathway could inform future treatments for excessive inflammation
Schematic representation of the newly described FGL-1/LAG-3 regulatory pathway: The liver-derived protein fibrinogen-like protein 1 (FGL-1) can inhibit T-cell activity via the immune regulator LAG-3, thereby helping to regulate excessive inflammatory responses.
Researchers at the University Medical Center Hamburg-Eppendorf (UKE), including several scientists from the German Center for Infection Research (DZIF), have worked with colleagues at the University of Basel to identify a previously understudied immune regulatory pathway that helps control inflammatory responses. The pathway involves the liver-derived protein FGL-1, which inhibits T-cell activity by interacting with the immune regulator LAG-3. T cells are white blood cells that play a key role in the immune system. The findings were published in Communications Medicine.
"The signaling pathway discovered by our team appears to play a central role in regulating excessive inflammatory responses. What we find particularly exciting is that the significance of this FGL-1/LAG-3 regulatory loop is likely to extend far beyond COVID-19," says lead author Dr. Sophia Cichutek from the Second Department of Internal Medicine at the UKE.
By analyzing samples from patients with COVID-19, the researchers found that elevated FGL-1 levels are associated with a stronger inflammatory response and a more severe course of the disease, and likely reflect a form of immunological counterregulation due to overactivation. The findings not only provide new insights into the pathophysiology of severe viral infections but also suggest new approaches to immunomodulatory treatment for COVID-19 and other diseases characterized by excessive inflammatory responses.
"Since FGL-1 is produced in the liver and is involved in regulating immune responses, our study also opens up new avenues for understanding and treating liver inflammation as well as other diseases characterized by dysregulated immune activation," says Prof. Dr. Julian Schulze zur Wiesch, clinician-scientist at the UKE and researcher at the DZIF.
The study was conducted within the Collaborative Research Center (CRC) 1648 "Emerging Viruses: Pathogenesis, Structure, and Immunity." The consortium is coordinated by the UKE and brings together 26 researchers from nine institutions in Hamburg, Germany, and Switzerland. Several scientists from the DZIF Hamburg-Lübeck-Borstel-Riems partner site contributed to the publication.
Source: Press release of the University Medical Center Hamburg-Eppendorf (in German)
