In a major scientific breakthrough, researchers from the Lions Eye Institute and Monash University have discovered a tissue protein that acts as a central ‘traffic controller’ for immune cells and can be hijacked by a virus to weaken immune responses. The discovery could drive new treatments for autoimmune conditions.
Pictured from left to right: Sheridan Daly, Peter Fleming, Professor Mairapia Degli-Esposti and Dr Valentina Voigt
Published today in Nature, the study discovered a key mechanism that controls how immune cells coordinate their responses, and how a common virus can sabotage it.
The research reveals that a molecule called CD44 centrally controls the network of support cells that guide immune system function.
Within this network of support cells, stromal cells help immune cells move efficiently and exchange the information needed to fight infections, respond to vaccines, and maintain overall health.
In a landmark finding, the research team discovered that cytomegalovirus (CMV) can hijack this system by producing a protein that blocks CD44 function on stromal cells, derailing immune cell traffic at its source and weakening the body’s antiviral response.
Lead researcher Professor Mariapia Degli-Esposti, Head of Experimental Immunology at the Lions Eye Institute (LEI) and Head of Experimental and Viral Immunology at Monash Biomedicine Discovery Institute (BDI), said the findings fundamentally change how scientists understand the signals that shape immune function.
“Think of the immune system like a busy city with millions of cells patrolling to keep us safe,” said Professor Degli-Esposti. “CD44 acts as the central traffic controller; it keeps immune cells moving and coordinates their interactions at the right place and time.”
Imagery of stromal networks
“Our study identifies CD44 as a master regulator of immune cell movement and communication and shows that viruses can undermine immunity not only by attacking immune cells directly, but also by targeting the essential tissue infrastructure they rely on.”
“This is a completely new way for a virus to target an immune response”.
This work redefines how immune responses are initiated and regulated by identifying stromal CD44 as a previously unrecognised checkpoint.
What this means for future breakthroughs in health and disease
Co-lead researcher Dr Chris Andoniou, a Senior Research Fellow at Monash BDI and the LEI, said the findings have wide-ranging implications for human health.
“Because CD44 plays such a central role in regulating immune activity, drugs inspired by the viral protein identified in this study could be developed to precisely dampen harmful inflammation,” he said.
“By learning from the virus, we may be able to design therapeutic molecules that safely reduce excessive immune activation, which could ultimately help manage and treat autoimmune conditions. We are still in the early stages, but this is an exciting development.”
Collaborative science drives innovation
The discoveries stem from major scientific efforts led by Professor Degli-Esposti’s team at LEI and BDI. First author Dr Xavier Sng, Research Fellow at BDI, conducted innovative experimental work that revealed how stromal CD44 functions within the immune network. Complementary studies by Dr Valentina Voigt at the LEI demonstrated that the CMV protein binding CD44 impairs antiviral T cell responses.
Pictured left to right: Dr Valentina Voigt, Sheridan Daly, Professor Mariapia Degli-Esposti, Dr Matthew Wikstrom and Peter Fleming
The work was enabled by strong interdisciplinary collaboration. By combining unique expertise in immune cell biology, the researchers linked molecular mechanisms to immune system function, highlighting the power of collaborative science to drive innovation.
The team pictured left to right: Dr Xavier Sng, Professor Mariapia Degli-Esposti and Dr Chris Andoniou
This research was supported by funding from the Australian Research Council and the National Health and Medical Research Council.
Read the paper “Fibroblastic reticular cells direct the initiation of T cell responses via CD44” in Nature at https://doi.org/10.1038/s41586-025-09988-8.
About the Lions Eye Institute:
For more than 40 years, the Lions Eye Institute has been at the forefront of global vision research and innovation, transforming the lives of patients through pioneering treatments. The Institute’s dedicated team of experts provides safe, effective and world-class eye care across Western Australia. To date, the Lions Eye Institute has delivered more than one million consultations, supporting its mission to achieve better vision for all.
About the Monash Biomedicine Discovery Institute:
Committed to making the discoveries that will relieve the future burden of disease, the Monash Biomedicine Discovery Institute (BDI) at Monash University brings together more than 120 internationally-renowned research teams. Spanning seven discovery programs across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection, Immunity, Metabolism, Diabetes and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.
