The findings, published in ‘Molecular Cell’, a peer-reviewed scientific journal on molecular and cell biology, throws new light on a protein receptor, C5aR2, that plays an important role in the moderation of many immune and inflammatory processes and explores its use as a potential therapeutic target for treating multiple chronic inflammatory diseases.
The research saw international collaboration between Professor Arun Shukla, IIT Kanpur, India with researchers Asuka Inoue, Tohoku University, Japan and Stéphane A. Laporte, McGill University, Canada.
This is the first time that researchers have identified key molecules within the immune system that may help fight the inflammation that drives chronic inflammatory diseases.
The findings of the research will help further research in novel drug molecules that can act on the receptors for C5a, a potent immune molecule that is linked to multiple immune-linked inflammatory diseases such as cancer, rheumatoid arthritis, sepsis and even COVID-19.
Prof. Abhay Karandikar, Director, IIT-K said “The publication of the research paper on inflammatory diseases is testament to the capabilities of IIT Kanpur to undertake challenging research at the frontiers of science. We are optimistic that the findings will lead to new light in the fight against chronic inflammatory diseases.”
UQ Prof. Trent Woodruff said the research investigated the part of the immune system responsible for the body’s natural response to pathogens and injury, known as the ‘complement system’. He said, “When activated inappropriately, the system drives inflammatory diseases such as sepsis, COVID-19, stroke, heart attacks, cancers and brain illnesses. It’s been really challenging for researchers to understand how this protein is activated due to its unusual structure.”
“Instead of coupling with cell-signalling proteins, C5aR2 relies on signal regulating proteins known as β-arrestin proteins. Our study investigated interactions between the C5aR2 and β-arrestin proteins, while screening for molecules that activated a connection between the two. We found key and specific cell signals present when the C5aR2 was activated, which may act to boost the immune system’s response in inflammation,” added Prof. Woodruff.
Co-investigator Professor Arun Shukla said the findings provided a framework for further exploration of β-arrestin proteins for their therapeutic modulation in disease. “We are now working to progress these research findings into disease models and potentially enable scientists to design novel drug molecules targeting C5aR2 to treat inflammatory disorders”.
Link to the paper: https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00741-3
