A new study in Nature Communications reveals how immune cells rapidly shut down their response after activation, preventing damage to healthy tissue. Researchers from Karolinska Institutet, sheds light on a molecular 'kill switch' that could help control infections or autoimmune diseases.
When T cells, a type of immune cell, detect infection or cancer, they activate quickly and produce cytokines - chemical messengers that fight threats. This process depends on messenger RNA (mRNA), which carries genetic instructions for making proteins. But once the danger passes, T cells must stop producing cytokines just as fast to avoid harming the body.
Researchers have discovered that many mRNAs in T cells carry two distinct shutdown signals. One is an AU-rich element - a stretch of genetic code that attracts proteins to degrade the mRNA. The other is a chemical tag called m6a methylation, which marks the mRNA for removal. When both signals appear together, the mRNA is broken down rapidly, halting the immune response.
"Our immune system has to strike a very fine balance: too little activation and disease takes over, or we can develop cancer; too much activation and it starts attacking the body, in what's known as autoimmunity," says Randall Johnson, professor at the Department of Cell and Molecular Biology , Karolinska Institutet.
The findings suggest that manipulating these signals could help boost immunity against infections or cancer, or dampen it in autoimmune conditions. "This system allows the immune system to keep the balance between under-activation and over-activation, making sure T cells operate within a narrow range," adds Randall.
The study was led by Randall Johnson of the Karolinska and Jernej Ule at the Francis Crick Institute, with contributions from the Sanquin Research Foundation in Amsterdam and the NOVA University in Lisbon. It was funded by support from the UK Dementia Research Institute, the Knut and Alice Wallenberg Foundation, the Wellcome Trust as well as other international research grants.
Publication
Paulo A. Gameiro, Iosifina P. Foskolou, Yumna A. Butt, Aniek A. M. Martens, Klara Kuret Hodnik, Igor Ruiz de los Mozos, Nordin D. Zandhuis, Žan Hozjan, Veronica M. Kot, Rupert Faraway, Michiel Vermeulen, Monika C. Wolkers, Randall S. Johnson & Jernej Ule
Nature Communications volume 17, Article number: 160 (2026)
