Protein identified as central to immune system

Researchers from the Walter and Eliza Hall Institute (WEHI) have identified what they believe is the one protein without which one of the body's key groups of immune cells cannot function.

When foreign invaders such as viruses attack the body, dentritic cells (DC) present the proteins from these intruders to the killer T cells of the immune system which allows for a full immune response to be targeted at the invaders.

In a study published in the journal Immunity, the researchers showed that a protein called PU.1 is essential for the development of these dentritic cells.

It is already known that the molecule Flt3 is important for this process to occur. Flt3 is a cytokine receptor found on the surface of blood stem cells and the parent cells that give rise to DC. However, until now very little has been known about how Flt3 is controlled.

What the team at WEHI has been able to show is that the transcription factor PU.1 can directly bind to the Flt3 gene to regulate its expression.

“PU.1 can therefore control DC development through regulating Flt3,” said project leader Dr Li Wu. This means, for instance, that if PU.1 is poorly regulated there is a deficiency in the development of blood cells and leukaemia can result.

“To study the role of PU.1 and look at how it’s regulated we developed an animal model and a new in vitro system for tracing DC development from their precursors,” explained WEHI’s Dr Sebastian Carotta. “These systems make it possible to switch off PU.1 in the precursor cells to DC. From that we determined that loss of PU.1 completely abolished DC development.”

Dr Wu said that while there have been a number of transcription factors linked to the development of specific dendritic cell populations, “this is the first time a single transcription factor has been shown to be required for all DC lineages”.

The findings of the study could lead to improved therapies, for instance for cancer patients with suppressed DC function for whom it may be possible to create new therapies employing different types of DC populations.

The study was supported by the National Health and Medical Research Council (NHMRC) of Australia, the Australian Research Council, the Leukaemia Foundation and Pfizer Australia.