www.science.org/doi/10.1126/...

Huge thanks to our collaborators and the patients who donated samples making this research possible! 🙏

#ScienceSignalingResearch #Immunology #IBD #UlcerativeColitis #SystemsBiology

Beyond UC, this methodology can be applied to other immune-mediated inflammatory diseases (IMIDs) to reveal cytokine network dynamics and potentially highlight novel therapeutic targets.

TL1A emerged as an upstream regulator of both TNF and IL-23A. Since drugs already target those downstream cytokines, TL1A is a promising target that could disrupt multiple inflammatory pathways simultaneously.

Several cytokines showed altered interactions across disease states: IL-22, TL1A, IL-23A, and OSM. We also predicted which JAK family members mediate specific cytokine-cytokine interactions.

We discovered a cytokine subnetwork unique to treatment-naive UC patients, the inflammatory landscape changes once treatment begins.

To validate our predictions, we used patient-derived colonic organoids and organoid-ILC cocultures to test whether predicted cytokine-cytokine interactions actually occur in a physiologically relevant system.

We used systems immunology to analyse single-cell RNA-seq data from colonic biopsies of treatment-naive patients, treatment-exposed patients, and healthy donors, building cytokine interaction networks across disease states.

Our findings reveal how the cytokine network gets "rewired" in UC and highlights TL1A as a key upstream regulator of TNF and IL-23A, cytokines already targeted by approved drugs. This could inform therapeutic strategies.