WEHI Wednesday Seminar hosted by Professor Jason Tye-Dine

Olivia Moscatelli
PhD Student – Tye Din Laboratory, Immunology division, WEHI

(This is a PhD Completion Seminar)

More Than a Gut Disease: Interleukin-2 and Translational Biomarkers in Coeliac Disease

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session

Followed by refreshments in the Tapestry Area

Coeliac disease is a common immune illness that remains substantially underdiagnosed, and there are still no approved therapies beyond a gluten-free diet. At the same time, an expanding clinical trial pipeline is creating urgent demand for better tools to diagnose disease, detect gluten-specific immune activity, and monitor treatment response.

An important unmet need is for clinical tools better suited to this purpose. Coeliac disease is still primarily diagnosed through the small intestinal damage it causes. In practice, the tools we rely on, serology and histology, measure the downstream consequences of disease rather than the immune response that drives it. They depend on ongoing gluten exposure, established tissue injury, and chronic immune activation, which limits their utility for both diagnosis and therapeutic development.

Gluten-specific CD4⁺ T cells are central to coeliac disease pathogenesis, coordinating inflammatory responses within the intestinal mucosa and beyond. Yet despite their central role, we still lack clinically useful biomarkers that directly capture this pathogenic immune activity.

In this thesis, I ask whether coeliac disease can be measured in a way that is closer to its underlying biology, through the early immune signals triggered by acute gluten exposure. I focus on interleukin-2 (IL-2), a cytokine released rapidly following antigen recognition, as a candidate biomarker of gluten-specific T-cell activation. I evaluate IL-2-based assays, particularly a whole blood assay, as potential diagnostic and pharmacodynamic tools for detecting gluten-specific immunity without the need for prolonged gluten challenge. I also examine the biological basis of IL-2 release and investigate how early systemic immune signals relate to intestinal immune responses following acute gluten exposure.

Overall, my work argues that coeliac disease is more than a disorder of intestinal injury. It is a systemic immune disease that may be better understood by measuring the signals that initiate the response rather than the tissue damage that follows.

All welcome!