(Vienna, 24-06-2025) An interdisciplinary research team from the Medical University of Vienna, in collaboration with the University of Vienna, found that targeted modification of a single protein in certain immune cells reduces intestinal inflammation in a mouse model of colitis. The study, currently published in the Journal of Experimental Medicine, focuses on the protein filamin A, whose structure can be modified by so-called RNA editing. The findings open up new perspectives for the development of therapeutic options for chronic inflammatory bowel diseases such as ulcerative colitis.
The research group led by Cornelia Vesely (Center for Anatomy and Cell Biology, MedUni Vienna), Riem Gawish (Department of Medicine I, MedUni Vienna) and Fatima C. Pereira (University of Vienna) investigated the role of filamin A in intestinal inflammation as part of the study. Filamin A is a protein that controls important processes within cells. In tissue, it can occur in a modified form that differs from the original form by a single amino acid. The modification is caused by RNA editing, a natural process in which certain building blocks of RNA (the carrier of genetic information from the cell nucleus to the protein) are specifically altered. While this modified form of filamin A is particularly abundant in healthy intestines, its levels decrease significantly in the course of acute colitis.
The researchers have now been able to show that a selective modification of filamin A induced at the RNA level has a protective effect: analyses in a mouse model for ulcerative colitis revealed less tissue damage and a milder overall clinical picture. This effect could not be explained solely by differences in the intestinal flora or intestinal structure cells, but was due to altered reaction patterns of the immune cells.
"According to our observations, the targeted introduction of modified filamin A into certain immune cells – neutrophils and macrophages – has a particularly positive effect on the course of the disease," reports first author Riem Gawish from the research team. "Since RNA can now be specifically edited using modern biotechnological methods, these findings reveal a new, targeted approach for the treatment of chronic inflammatory bowel diseases: controlled RNA editing to specifically attenuate harmful immune responses while preserving essential immune functions," says study leader Cornelia Vesely, summarising the significance of the study results.
In ulcerative colitis, inflammation of the intestinal mucosa typically spreads in episodes starting in the distal colon, is often difficult to treat, and severely impaires the quality of life for patients. The exact causes of this form of chronic inflammatory bowel disease are not fully understood. In addition to genetic risk factors, environmental influences, changes in the intestinal flora (microbiome) and a disturbed barrier function of the intestinal mucosa are considered to be key triggers. The new findings now provide novel insights into the role of cellular RNA processing in the course of the disease and will be confirmed in further studies.
Publication: Journal of Experimental Medicine
Filamin A editing in myeloid cells reduces intestinal inflammation and protects from colitis.
Riem Gawish, Rajagopal Varada, Florian Deckert, Anastasiya Hladik, Linda Steinbichl, Laura Cimatti, Katarina Milanovic, Mamta Jain, Natalya Torgasheva, Andrea Tanzer, Kim De Paepe, Tom Van de Wiele, Bela Hausmann, Michaela Lang, Martin Pechhacker, Nahla Ibrahim, Ingrid De Vries, Christine Brostjan, Michael Sixt, Christoph Gasche, Louis Boon, David Berry, Michael F. Jantsch, Fatima C. Pereira and Cornelia Vesely
https://doi.org/10.1084/jem.20240109