Highlights of IMMUNOLOGY2026™ - Invited Program Recordings-Peripheral immune signatures that orchestrate complex behavior

Peripheral immune signatures that orchestrate complex behavior

Video Transcription

Video Summary

Dr. Michael Wheeler described his lab’s work on how peripheral immune signals shape behavior, especially in depression and stress. He argued the brain should be viewed like a mucosal tissue with immune interfaces, including the meninges. In mouse models of chronic stress, his team found increased inflammatory cytokines, immune-cell recruitment to the meninges, and heightened fear-like behavior. Transferring inflammatory monocytes was enough to worsen anxiety and fear, while depleting them reduced these behaviors. They identified IL-1β as a key mediator reaching the amygdala and acting on astrocytes, where EGFR signaling normally helps suppress inflammation. Knocking down astrocytic EGFR increased fear behavior. They also found that psychedelics such as psilocybin and MDMA reduced meningeal immune-cell recruitment, likely through effects on tissue and vascular remodeling, and rescued behavior. Finally, psilocybin pre-treatment protected mice from DSS colitis, suggesting broader anti-inflammatory effects beyond the brain.

Keywords

peripheral immune signals

chronic stress

meningeal immune cells

IL-1β signaling

astrocytic EGFR

psilocybin anti-inflammatory effects