Université de Strasbourg

Roméo Ricci: Discovery of a new inflammation-control mechanism

30 March 2023

Image - Rossella Venditti & Antonella de Matteis, Tigem, Naples

Immunology: discovery of a new inflammation-control mechanism

To eliminate any looming dangers, our body creates a frontline defence mechanism, inflammation. In a study published in Nature Immunology, Romeo Ricci’s team at the Institute of Genetics and Molecular and Cell Biology (IGBMC-CNRS/Inserm/Unistra) has demonstrated a novel mechanism of inflammation initiation in immune cells in response to pathogens and tissue damage. This discovery opens up new therapeutic prospects.

Our cells contain many compartments with quite distinct functions. Among these are endosomes, which are small vesicles formed by the replication and pinching of the cell membrane. The endosomes allow nutrients and other molecules from the extracellular area to be imported into the cell. Molecules from pathogens can thus be found inside these endosomes. The presence of such pathogen agents triggers an inflammatory response in our cells, which should enable them to be eliminated. But how?

In order to understand this, scientists are looking into the way in which these danger signals affect the composition of the endosomes. In this study, Romeo Ricci’s team, together with a team from the Telethon Institute of Genetics and Medicine (Italy), demonstrate that numerous danger signals modify the membrane composition of these vesicles in such a way that they can be bound by a molecule known as NLRP3.

Assembly of a protein complex

Binding NLRP3 to endosomes leads to the assembly of a protein complex, the inflammasome, which induces the release of inflammatory factors at the source of the inflammatory response.

NLRP3 inflammasome activation is significant in many common inflammatory conditions, such as chronic inflammation in arthritic gout, Alzheimer’s disease, and type 2 diabetes. The discovery of this mechanism therefore provides new therapeutic prospects.

Roméo Ricci was a 2017 USIAS Fellow. An important basis of the research featured was developed in his 2-year Fellowship, pioneering a highly innovative experimental framework. This made possible the study of the molecular architecture of the NLRP3 inflammasome in intact cells, a long-standing challenge in the field.

This news was originally published in French in Savoir(s), the University of Strasbourg's news corner.

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