JOINT PRESS RELEASE OF THE EBERHARD KARLS UNIVERSITY OF TÜBINGEN AND THE UNIVERSITY OF HOHENHEIM

Universities of Tübingen and Hohenheim discover previously unknown peptide that prevents overreaction of the immune system in tomato plants

Tomato plants possess a sophisticated system to protect themselves against herbivores: the signaling peptide Systemin triggers a cascade of plant defense responses. A research team from the University of Tübingen and the University of Hohenheim in Stuttgart has now discovered that tomato plants possess a previously unknown natural Systemin antagonist named antiSys. AntiSys prevents the defense system from overreacting, which would otherwise interfere with plant growth and reproduction. This discovery expands our understanding of plant immunity and demonstrates that not only defense signals, but also their natural antagonists, are crucial for balancing growth and defense. The study is a result of a collaboration within the Collaborative Research Center (CRC) 1101 “Molecular Encoding of Specificity in Plant Processes.” The results have been published in the renowned journal "Cell": https://doi.org/10.1016/j.cell.2025.07.044

Solanaceous plants, such as tomatoes, have a remarkably fine-tuned defense system protecting them from pests and pathogens. The signaling molecule Systemin plays a central role in this process. When, for example, insects cause feeding damage, Systemin triggers cellular defense reactions. The plant then produces substances that specifically impair the digestive system of their attackers, so that they can no longer utilize the ingested nutrients.

However, similar to the human immune system, constant or uncontrolled activation is dangerous. It can severely compromise normal growth and development.


AntiSys blocks Systemin receptor

The research team has now discovered a previously unknown antagonist of Systemin: the peptide antiSys. This small protein resembles Systemin in its structure but acts as an inhibitor of the highly sensitive Systemin receptor SYR1.

“AntiSys binds to the same receptor as Systemin, but without activating it. Since antiSys predominates in healthy plants, it occupies the receptor and thereby makes sure that the immune system remains inactive,” explains Professor Andreas Schaller from the University of Hohenheim. “However, when the plant is attacked by insects, Systemin is formed and released in large amounts. This leads to a competitive displacement at the SYR1 receptor: Systemin binds, the receptor is activated, and immune responses are triggered.”


AntiSys keeps immune responses under control

The importance of antiSys is demonstrated by plants that lack this peptide. Using CRISPR/Cas9 technology, the researchers generated mutants that did not produce antiSys. These plants showed significantly reduced growth, produced fewer fruits, and in some cases exhibited drastic malformations.

“These effects result from the uncontrolled activation of the immune system. If antiSys as an antagonist is missing, even the smallest amounts of Systemin are sufficient to activate the receptor and initiate defense responses,” says the head of the study, Professor Georg Felix from the Center for Plant Molecular Biology (ZMBP) at the University of Tübingen. “However, if we also remove the receptor, plants remain healthy despite the absence of antiSys.”


Tomatoes have several activating Systemins–and antiSys

But antiSys was not the only new finding: “For a long time, it was believed that Systemin is the only molecule of its kind in solanaceous plants. We have now found that, in addition to the Systemin gene, there is an entire gene cluster in tomato encoding four structurally similar peptides (or their precursor proteins),” says Lei Wang, who made this discovery as a doctoral student in Professor Felix’s lab.

“Three of these peptides resemble Systemin in their activity: they also trigger immune responses. Only antiSys—and this is the most exciting aspect—has exactly the opposite function: the antagonist suppresses immune responses.”

The researchers found antiSys also in related solanaceous crops such as eggplant, potato, and pepper, indicating an important function conserved throughout evolution. “Our discovery raises the question of whether similar antagonists also exist in other plant species—and whether they could be specifically used to make crop plants more resistant while maintaining vigorous growth,” says Professor Felix.


Parallels to the human immune system

The researchers see striking parallels to the human immune system, in which special antagonists dampen the effects of activating cytokines in order to keep inflammatory responses in balance. If the antagonist is missing, the balance is disturbed, resulting in autoimmune diseases such as rheumatoid arthritis or chronic inflammatory bowel diseases like Crohn's disease and ulcerative colitis.

In tomatoes, antiSys fulfills this task by maintaining the balance between defense and healthy growth: “Without antiSys, growth and development become disrupted, similar to a chronic inflammatory reaction: the receptor is ‘accidentally’ activated, leading to immune responses even though there is no insect attack,” explains Professor Felix.


Publication
Wang et al., A receptor antagonist counterbalances multiple systemin phytocytokines in tomato, Cell (2025), https://doi.org/10.1016/j.cell.2025.07.044