Skip to main content
Domnica Luca AG Kato

News categories: Publication

Dysregulation of T cell homeostasis

Dysregulation of regulatory T cell homeostasis by ADAR1 deficiency and chronic MDA5 signaling

The research team of Prof. Dr. Hiroki Kato at the Institute of Cardiovascular Immunology is dedicated to understanding the intricate mechanisms of immune responses in the context of viral infections and autoimmune diseases. They are particularly interested in exploring how cytoplasmic RNA sensors, like MDA5, differentiate between viral RNAs and self-RNAs, initiating type I interferons (IFNs) as anti-viral defense. However, mutations in MDA5 can lead to autoimmune diseases. Complementary to that, Domnica Luca et al. recently published her findings in Science Advances with the title "Dysregulation of regulatory T cell homeostasis by ADAR1 deficiency and chronic MDA5 signaling."


Abstract: ADAR1 deficiency constitutively activates MDA5 and causes type I IFN-driven autoimmune diseases. We found a significant reduction in the regulatory T cell (Treg) population in patients with type I interferonopathies caused by mutations in the ADAR1 or IFIH1 gene, encoding MDA5. We analyzed the underlying mechanisms using murine models and found that Treg-specific Adar1 deletion caused peripheral Treg loss and scurfy-like lethal autoimmune disorders. Treg-specific expression of MDA5 gain-of-function mutant also reduced the peripheral Treg population via apoptosis, resulting in severe autoimmune symptoms. However, shut-down of MDA5 signaling in Adar1-deficient Tregs still induced eIF-2α-mediated protein synthesis shut-off, leading to Treg loss and lethality. Altogether, our results highlight the dysregulation of Treg homeostasis in Adar1 deficiency as a key determinant for type I interferonopathies.

Publication:

Luca, D., et al. (2024)

Dysregulation of regulatory T cell homeostasis by ADAR1 deficiency and chronic MDA5 signaling

Science Advances

DOI: 10.1126/sciadv.adk0820

Related news

Kathrin Leppek Publication PM

News categories: Publication

Starting points for the control of protein synthesis

Bonn researchers develop a versatile toolbox for the characterization of IRESes in cells.
View entry
Pandyra Publication Graphical Abstract

News categories: Publication

Genetic mutation affects survival after viral infection

Scientists discovered that haploinsufficiency in the Pax5 gene affects antiviral responses. The study was led by Prof. Dr. Aleksandra Pandyra from the Institute of Clinical Chemistry and Clinical Pharmacology at the University Hospital Bonn in collaboration with Prof. Dr. Arndt Borkhardt, Clinic Director at the Pediatric Oncology at the University Hospital Düsseldorf. The findings were published in the latest edition of EMBO Molecular Medicine.
View entry
AG Kürthen Multiple Sclerosis Bonn

News categories: Publication

Potential target for MS therapy discovered

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by the immune system. B cells, which are a type of white blood cell, play a role in the development of MS and are thus a target for therapies. Researchers at the University Hospital Bonn (UKB), the University of Bonn and the FAU Erlangen-Nuremberg identified the membrane protein MLC1 as a potential target antigen in MS. The results of the work have now been published in the renowned journal “Neurology Neuroimmunology & Neuroinflammation”.
View entry

Back to the news overview