IMMUNOLOGY2024™ Conference Recordings-A dynamic paracrine FGF21-mTORC1/mTORC2 signaling axis regulates thymus function across the lifespan

A dynamic paracrine FGF21-mTORC1/mTORC2 signaling axis regulates thymus function across the lifespan

Video Transcription

Video Summary

The speaker, Sarah Wedemeyer, presented work on thymic aging and regeneration, using differential gene expression mapping to study thymic stromal cells without disrupting their biology. Her lab focused on FGF21, a hormone known to affect metabolism and adiposity, and asked whether thymic FGF21 from medullary stromal cells could improve thymus function through mTOR signaling. They created a thymus-specific FGF21 knock-in mouse and found increased thymic cellularity with age, enhanced mTORC1 during early growth and mTORC2 later in life, improved peripheral naive T-cell ratios, and better resistance to influenza infection. The mice also showed improved clonal deletion, reduced autoimmunity markers, and larger cortical stromal cell size during aging. Overall, the data suggest that local FGF21 signaling helps preserve thymus structure, T-cell production, and immune tolerance in aging.

Keywords

thymic aging

FGF21 signaling

mTOR pathway

thymus regeneration

T-cell immunity