{ "title": "An inside look at a molecular switch that triggers inflammation ", "modified_at": "2026-11-09 08:24:25", "published_at": "2026-11-09 08:24:00", "url": "https://press.vib.be/an-inside-look-at-a-molecular-switch-that-triggers-inflammation", "short_url": "http://prez.ly/QAoe", "culture": "en", "language": "EN", "subtitle": "Ghent, 9 November 2026 \u2013 Researchers at VIB and Ghent University have uncovered how an important driver of inflammation is activated at the molecular level. Their findings, published in Science Immunology, also explain how a medicine used to treat a severe form of psoriasis blocks this inflammatory signal.", "slug": "an-inside-look-at-a-molecular-switch-that-triggers-inflammation", "body": "

Inflammation is an essential part of the body’s defense against infection and injury. But when inflammatory signals become too strong or poorly controlled, they can contribute to diseases such as psoriasis.

One important player is the IL-36 receptor, a protein that helps cells respond to inflammatory signals. Researchers led by Dr. Danielle Clancy and Prof. Savvas Savvides (VIB-UGent Center for Inflammation research) have now revealed in unprecedented detail how this receptor is switched on.

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A molecular switch for inflammation

Using the VIB-VUB cryo-electron microscope, which allows scientists to visualize biological molecules at near-atomic resolution, the team captured the molecular machinery assembled around the IL-36 receptor to produce an inflammatory signal.

They discovered a surprising mechanism. An inflammatory molecule called IL-36γ initially attaches relatively weakly to the receptor. But that first contact makes it possible for another receptor component to join much more tightly, creating a stable complex that can trigger a strong inflammatory response.

“You might expect the strongest inflammatory signal to start with the tightest interaction, but that isn’t what we see here,” says first author Dr. Julie Andries. “It is the way the different pieces come together that ultimately determines how effectively the signal is passed on.”

The researchers also studied a related immune molecule called IL-37 and found an almost opposite pattern. IL-37 attaches much more strongly to the IL-36 receptor but is less effective at completing the signaling complex. As a result, it produces a weaker inflammatory response than IL-36γ.

“What this study shows is that triggering inflammation is not simply a matter of a molecule binding to a receptor,” says Dr. Clancy. “Different molecules can use the same receptor in very different ways, and those differences can have a major impact on the inflammatory response.”
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Explaining how a psoriasis therapeutic works

The findings also help explain how spesolimab, an antibody used to treat severe psoriasis, interferes with this inflammatory pathway.

Rather than simply covering the site where IL-36γ binds on the IL-36 receptor, spesolimab engages the IL-36 receptor elsewhere. This results in a surprising restructuring of the IL-36 receptor that prevents IL-36γ from engaging with the receptor, effectively stopping the inflammatory signal.

“Seeing these interactions at the molecular level helps us understand both sides of the process: how the inflammatory signal is switched on and how it can be switched off,” says Prof. Savvides.

The findings provide more than a snapshot of how the IL-36 receptor works; they offer a blueprint for investigating how this pathway behaves across different inflammatory conditions and how it might be targeted. By understanding the rules that determine whether an inflammatory signal becomes strong, weak, or blocked altogether, researchers now have a more concrete foundation for exploring more precise approaches to controlling harmful inflammation.

Publication

The structural basis of IL-36R proinflammatory signaling mediated by IL-36γ and IL-37. Andries et al. Science Immunology, 2026.

Funding

The research was supported by the Research Foundation Flanders (FWO), the Marie Sk\u0142odowska-Curie Actions program of the European Union, and VIB.

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\"Gunnar
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\n Gunnar De Winter\n Science Communication Manager, VIB\n \n
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\"Kristof
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\n Kristof Windels\n Media Relations Manager, VIB\n \n
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