Article Synopsis
- The thymus is crucial for adaptive immunity but shrinks with age, leading to weaker immune responses.
- Researchers identified two new types of thymic epithelial cells (TECs) in aging that form dense clusters and lack thymocytes, worsening with age.
- This study reveals how these age-associated TECs disrupt regeneration and repair processes in the thymus, potentially guiding future therapies to enhance immunity in older adults.
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Article Abstract
The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTECs expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune-boosting therapies in older individuals.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362016 | PMC |
| http://dx.doi.org/10.1038/s41590-024-01915-9 | DOI Listing |
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