IMMUNOLOGY2025™ Conference Recordings-T cell differentiation in disease and tissues

Video Transcription

Video Summary

The speaker thanks AAI for the award and shares a humorous story about nearly missing it because of overdue membership dues. He then thanks his wife, family, mentors, collaborators, and many trainees, emphasizing that his scientific accomplishments are the result of a large community, not just his own work.<br /><br />He highlights three main research themes from his lab. First, his lab discovered the TIM family, especially TIM-3, initially identified on Th1 cells. TIM-3 later became known as a checkpoint molecule involved in T-cell exhaustion and tumor immunity, and blocking TIM-3 with PD-1 can improve anti-tumor responses. He also shows that TIM-3 is highly expressed on microglia in the brain, where it helps regulate TGF-β signaling and limits phagocytosis; deleting TIM-3 in microglia reduces amyloid burden and improves cognition in Alzheimer’s models.<br /><br />Second, he discusses Th17 cells. His lab showed that not all Th17 cells are pathogenic: some are homeostatic in the gut, while IL-23 can convert them into inflammatory, encephalogenic cells. A key mechanism is that IL-23 phosphorylates glucocorticoid receptor, preventing it from entering the nucleus and allowing inflammatory genes to remain active.<br /><br />Third, he presents neuro-immune interactions in allergy and gut immunity. Cytokines such as IL-4 and IL-13 act on enteric neurons to induce neuropeptides like NMU, while neuronal signals shape immune responses. Deleting IL-13 receptor in enteric neurons impairs worm expulsion and alters gut neuron maintenance, revealing a two-way dialogue between the nervous and immune systems.

Keywords

TIM-3

immune checkpoint

T-cell exhaustion

microglia

Alzheimer's disease

Th17 cells

IL-23

neuro-immune interactions

gut immunity