Researchers from the Lions Eye Institute and Monash University have discovered a key mechanism that controls how immune cells coordinate their responses, and how a common virus can sabotage it.1,2 The discovery could drive new treatments for autoimmune conditions.
Published in Nature, 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.
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.”
“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.
the findings fundamentally change how scientists understand the signals that shape immune function
Breakthrough Knowledge
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.
This research was supported by funding from the Australian Research Council and the National Health and Medical Research Council.
Reference
- Scientists disover novel immune ‘traffic controller’ hijacked by virus. Available at org.au/about/news/scientists-discover-novel-immune-traffic-controller-hijacked-by-virus/?fbclid=IwY2xjawQN8VJleHRuA2FlbQIxMABicmlkETI3VVhJYlozTkZ1eXFhUnVEc3J0YwZhcHBfaWQQMjIyMDM5MTc4ODIwMDg5MgABHq8ykPI1oK2kc3l-mhZQ_NbH4nhYIcTLvo62Wy312rWgVwC1h8TcDEGeYQUG_aem_Mpu8vnk8d3Ob7k1nesX_Ug [accessed Mar 2026].
- Sng XYX, Voigt V, Schuster IS, et al.Fibroblastic reticular cells direct the initiation of T cell responses via CD44. Nature (2026). doi: 10.1038/s41586-025-09988-8
