Researchers target key protein to fight inflammatory disease

For the first time, researchers have identified key molecules within the immune system that may help fight the inflammation that drives chronic diseases including cancers, sepsis and brain disease.

The University of Queensland collaborated with the Indian Institute of Technology, Kanpur on the study.

UQ Professor 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’.

“When activated inappropriately, the system drives inflammatory diseases such as sepsis, COVID-19, stroke, heart attacks, cancers and brain illnesses,” Professor Woodruff said.

A key protein, known as C5aR2, is a potential therapeutic target for treating chronic disease, due to its ability to moderate many immune and inflammatory processes.

“It’s been really challenging for researchers to understand how this protein is activated due to its unusual structure,” Professor Woodruff said.

“Instead of coupling with cell-signalling proteins, C5aR2 instead 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”, Professor Woodruff said.

“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.”

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”.

This study is the journal Molecular Cell (DOI:10.1016/j.molcel.2021.09.007), as part of an international collaboration with Professor Arun Shukla, based in India, and researchers Asuka Inoue, based in Japan, and Stéphane A. Laporte in Canada.