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Preprint WatchModerateAugust 28th, 2026

Epithelial and γδ T cell CD47 have complementary yet distinct roles in regulating γδ intraepithelial lymphocyte migration

Parthasarathy A, Fischer MA, Parkos CA, Edelblum KL.

CD47 has compartment-specific and opposing roles at the intestinal epithelium, with epithelial CD47 restricting gamma delta intraepithelial lymphocyte motility and lymphocyte-derived CD47 promoting it, while conditional deletion on either compartment leaves lymphocyte composition unchanged.

Moderate contradiction

2 prior failures

Two documented clinical failures match this mechanism, or a single Phase 3 failure is on record.

CD47 blockade is usually modelled as a single do-not-eat-me axis, and this preprint reports that CD47 acts in opposite directions depending on which cell in the intestinal epithelium carries it. Claidex holds two CD47 failures. [[evorpacept-cd47-mss-metastatic-colorectal-cancer-phase2-safety-termination]] recorded a safety termination in refractory microsatellite stable metastatic colorectal cancer, the same tissue compartment this preprint studies, and [[magrolimab-cd47-classic-hodgkin-lymphoma-phase2-program-discontinuation]] recorded a programme discontinuation in classic Hodgkin lymphoma. A systemic antibody cannot distinguish epithelial CD47 from lymphocyte CD47, so opposing compartmental roles are a plausible contributor to the narrow therapeutic window seen in gut indications. The flag is moderate on failure count rather than archetype.

Abstract excerpt

Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IEL) continuously survey the intestinal epithelium to promote mucosal host defense. Although γδ IELs migrate in and out of the lateral intercellular space (LIS) between adjacent enterocytes, the molecular mechanisms governing their migratory behavior are incompletely understood. Based on the known role of CD47, or integrin associated protein (IAP), in mediating neutrophil transepithelial migration, we investigated whether CD47 expression reflects a conserved mechanism regulating γδ IEL surveillance behavior. Here, we report that conditional CD47 deletion on intestinal epithelial cells or γδ T cells had no effect on IEL composition. Using intravital imaging, we identified complementary roles for CD47 on γδ IELs and epithelial cells, with epithelial CD47 restricting γδ IEL motility and γδ T-cell-derived CD47 promoting cell migration. Further investigation revealed that both CD47 and CD18 contribute to γδ IEL surveillance behavior, although CD47 regulates γδ IEL migration in a CD18-independent manner.

Matching Claidex post-mortems

2 of 2 indexed

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.