Single-cell RNA sequencing of thymic EC and TEC from control and RANKL treated aged mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1010669 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25786847_1.fastq.gz | Fastqsanger.gz | |||
| SRR25786847_2.fastq.gz | Fastqsanger.gz | |||
| SRR25786848_1.fastq.gz | Fastqsanger.gz | |||
| SRR25786848_2.fastq.gz | Fastqsanger.gz |
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Project description:Age-related thymic involution is one of the major causes of immunosenescence, characterized by reduced production of naive T cells, leading to increased susceptibility to cancers, infections, autoimmunity and reduced vaccine efficacy. Here, we reveal that the RANK/RANKL axis is altered in the thymus during aging, which results in a decline in thymic epithelial cell (TEC) and endothelial cell (EC) function and, consequently, to thymic involution. Whereas RANKL neutralization in young mice mimics thymic involution, RANKL treatment in aged individuals restores the thymic architecture, TEC and EC functional properties, and thymic T-cell production. This cascade of events results in peripheral T cell renewal and effective anti-tumor and anti-viral immune responses. Furthermore, we provide the proof-of-concept that RANKL stimulates TEC and EC in human thymic organo-cultures. Collectively, our findings identify RANKL administration as a potent therapeutic strategy to rejuvenate thymic function and improve T-cell immune function in the elderly.
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