Research reveals switch in brain immune system evolution
22 January 2026
Researchers from Peter Mac and University of Melbourne have uncovered surprising new insights into how the brains immune system evolved.
The brain has its own resident immune cells that play crucial roles in neurological diseases and brain cancer, but how this brain immune system has been shaped by evolution has remained puzzling.
In a study published in Nature, a team led by Professor Ben Hogan explored a highly specialised population of cells that operate at the borders of the brain.
"The brain is separated from the rest of the immune system by the blood-brain barrier and meningeal membranes, which tightly control immune access and help make neurological diseases and brain cancers especially challenging to treat,” Professor Hogan said.
“The brain relies on specialised resident immune cells that clear waste, monitor damage and maintain a healthy tissue environment.”
In humans and other mammals, these immune cells include 'border-associated macrophages'; blood cells that clean wastes at the borders of our brains.
By studying zebrafish, sharks, amphibians, chickens, marsupials and mice, the collaborative team including researchers from Australian Regenerative Medicine Institute at Monash University, University of Queensland and the Cardiovascular Research Institute (Weill Cornell Medicine, New York) discovered that the cells patrolling brain borders have evolved twice.
While the other vertebrates analysed in the study use a type of lymphatic cell for waste clean-up and surveillance at the borders of their brain, a separate evolution event means a type of blood cell performs this role in humans and other mammals.
“In non-mammals, these cells come from the lymphatic vascular system rather than the immune system, yet they behave in remarkably immune-like ways,” Professor Hogan said.
“It shows the lymphatic vascular system is far more flexible and powerful than we previously appreciated. Excitingly, it suggests that we might one day be able to harness the immune-like potential of lymphatics to treat disease.”
The work is part of a larger program of research that aims to deeply understand the biology of brain barriers and find ways to bypass them to treat brain diseases and brain cancers.
Brain tumours and brain metastases often evade immunotherapy and anti-cancer drugs by hiding behind protective barriers and manipulating their local environment.
“We aim to deeply understand how brain barriers form, how they evolved and how they function. This will help us to find innovative ways to manipulate them for therapeutic gain in the future,” Professor Hogan said.
“This discovery on how the brain immune system changed throughout evolution was a serendipitous finding arising from this research program. We are excited that the work offers up new directions in lymphatic system research, an area emerging as increasingly important in brain health and disease.”
This work was supported by funding from the Australian Research Council and unveils new understanding in brain immune evolution and lymphatic biology.