AI Unlocks New Mechanisms in Crohn’s Disease

A UC San Diego report describes use of artificial intelligence to nominate a putative NOD2–girdin partnership that may shape macrophage fate and intestinal inflammation.

The findings are evidence that NOD2 directly binds girdin, a relationship the authors propose could stabilize immune regulation by limiting macrophage-driven inflammatory programs. The report also links common Crohn’s-associated NOD2 mutations to loss of this interaction and increased inflammatory macrophage activity.

The team used AI to screen thousands of macrophage gene-expression signatures for reproducible patterns and to prioritize candidate interacting partners; girdin was among the top-ranked modulators. Targeted experimental follow-up on AI-prioritized candidates is reported to have produced functional effects on bacterial sensing, inflammatory signaling, and tissue repair.

Restoring the NOD2–girdin axis or targeting downstream pathways is presented as a plausible therapeutic strategy—options could include small molecules or biologics that stabilize the interaction or shift macrophage phenotypes toward tissue repair. The evidence is mechanistic and preclinical; clinical translation will require rigorous target validation, toxicology and safety testing, and early-phase proof-of-concept trials. If validated in human studies, interventions that restore this interaction could enable mechanism-directed therapy for a subset of Crohn’s patients.