IMMUNOLOGY2026™ Conference Recordings For Attendees-Noncanonical role for Caspase-5 in the human intestinal epithelium

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Video Summary

Researchers discovered a new role for caspase-5, an inflammatory caspase thought to function mainly in immunity. They found that caspase-5 is expressed specifically in the intestinal tract, unlike caspase-4, which is broadly expressed. In human colonic organoids, caspase-5 exists as three isoforms, and the C isoform is the most active. Using protein interaction studies, they showed that caspase-5C binds Disheveled proteins and activates Wnt signaling. Mechanistically, caspase-5C requires its catalytic activity to cleave APC at D556, disrupting the beta-catenin destruction complex. This allows beta-catenin to accumulate and turn on Wnt target genes, promoting organoid growth and cell proliferation. Caspase-5C is enriched in the transient amplifying zone of the gut, where Wnt levels are low but needed for proliferation. In inflammatory bowel disease patients, caspase-5C and Wnt signaling are increased, suggesting a role in tissue repair and a potential therapeutic target.

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Date April 16, 2026 10:15 AM - 10:30 AM

Room 102

Session Innate Immune Defenses in the Epithelium

Speaker Yuhua Shi

Track Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

Year 2026

Keywords

caspase-5

Wnt signaling

beta-catenin

intestinal organoids

APC cleavage

April 16, 2026 10:15 AM - 10:30 AM

102

Innate Immune Defenses in the Epithelium

Yuhua Shi

Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

2026