Orphan GPR84 facilitates uropod de-adhesion at multiple steps during leukocyte extravasation.

GPR84 is essential for leukocyte uropod de-adhesion during extravasation, with deficiency causing flawed detachment in mice and Drosophila, impairing immune cell migration.

• Why it matters: Understanding the final steps of leukocyte extravasation is crucial for controlling immune responses and inflammation, yet the terminating signals involved are not well understood.
• What they did: The study combined high-resolution intravital imaging and cell-specific genetics to investigate GPR84 orthologs, revealing their role in actin regulation and cell adhesion during immune cell exit.
• The result: Loss of GPR84 impairs uropod detachment by disrupting Rho activation, and pharmacological blockade reduces immune cell migration, highlighting GPR84 as a potential therapeutic target for inflammatory diseases.