How the immune system “thinks” with acetylcholine

2019 - 02 - 25

T cells produce acetylcholine, classically known as a neurotransmitter in the brain, to be able to fight off viral infections. This is a novel ground-breaking finding from the laboratory of Prof Tak Mak at the Princess Margaret Cancer Centre, Toronto, Canada, to which LIH’s researcher Prof Dirk Brenner also contributed.

Prof Tak Mak - renowned for cloning the human T cell receptor – with his team and collaboration partners published a new study in February 2019 in Science providing the first proof-of-function findings for T cell-derived acetylcholine in antiviral immunity. Acetylcholine produced by T cells during viral infection was found to be essential to trigger vasodilation, allowing the immune cells to leave the blood stream to reach virus-infected cells in tissues.

The study solves a puzzle scientists have pondered for more than a century’, tells Prof Mak. He explains the main discovery in simple terms: ‘During infection, T cells synthesize acetylcholine. In the brain, acetylcholine functions as a neurotransmitter and controls learning and memory. In the immune system, T cells making this classical brain chemical are able to jump out of the blood circulation and take action in the tissues to fight infection.

It is truly astonishing that a neurotransmitter, which is secreted by T cells dilates blood vessels and slows down the bloodstream locally at the sides of infection.’ underlines Prof Dirk Brenner from the Experimental & Molecular Immunology research group in LIH’s Department of Infection and Immunity, who participated in the study.

The discovery was made when the team genetically engineered mice lacking the enzyme acetylcholine transferase in T cells, making them unable to produce acetylcholine. The researchers observed that the immune cells of these animals could not control chronic viral infections. ‘We now have absolute genetic proof that immune cells need acetylcholine,’ says Prof Mak. ‘We believe it is an entirely new lens though which to look at numerous diseases including viral infections, cancer and autoimmune conditions.

With respect to cancers, a tumour is often surrounded by immune cells that cannot break through its defences, possibly because they are not producing sufficient amounts of acetylcholine. In this case, strategies to increase immune neurotransmitter production may be beneficial. The flip side is at play in autoimmune diseases such as rheumatoid arthritis or multiple sclerosis, where the autoimmune T cells attack self-tissues. Here, a reduction in neurotransmitter signalling may quell the hordes of immune cells invading joints or the central nervous system.

The next research goal will be to identify and target the key receptors that facilitate the signalling crosstalk between immune cells and diseased organs.

The research was mainly funded by a grant from the Canadian Institutes of Health Research to Prof Mak, a Cancer Research Institute Irvington Postdoctoral Fellowship to first-author Dr Maureen Cox, and by The Princess Margaret Cancer Foundation. Prof Dirk Brenner is funded through an ATTRACT Consolidator grant by the Luxembourg National Research Fund (FNR).

This communication is based on a press release from the Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.

Read the publication Cox et al., 2019

Watch a video with Prof Mak explaining the findings.