Retinoic acid-driven expansion of CD16hiCD177+ neutrophils mediates steroid-resistant GI-GVHD.

Retinoic acid promotes expansion of CD177+ neutrophils that drive steroid-resistant GI-GVHD, with RA receptor inhibition restoring steroid sensitivity in models.

• Why it matters: Steroid-resistant GI-GVHD is a deadly complication lacking targeted treatments, and understanding neutrophil roles could reveal new therapeutic avenues.
• What they did: Single-cell RNA sequencing identified a CD16hiCD177+ neutrophil subset expanded in SR-GI-GVHD, with RA-driven programming via RARA-SPI1 axis; genetic and pharmacological interventions in mice confirmed their pathogenic role.
• The result: Targeting RA signaling reduced disease severity, improved survival, and re-sensitized to steroids, highlighting the RA-driven neutrophil subset as a promising therapeutic target.