Description
Background: Ageing is accompanied by intestinal barrier dysfunction due to increased endothelial permeability, permitting the translocation of bacterial products into the bloodstream. Concurrently, age-related thymic involution, tissue architectural distortion and microenvironmental modifications lead to reduced thymic emigration of naïve T cells and expansion of peripheral memory T cells. Nevertheless, the relationship between gut barrier disruption and T cell ageing is poorly understood.Methods: To address this, circulating markers of intestinal barrier dysfunction (occludin) were assessed in healthy young (n=40) and healthy old (n=55) adults. Older individuals were split into 2 cohorts: those with low microbial translocation (MT) (n=24) and those with high MT (n=31). Detailed immunophenotyping and transcriptomic analysis of peripheral immune cells were carried out in all participants. Features of thymic involution, including lipid deposition, stromal cell senescence and tissue architecture, were examined ex vivo in young and old wild type and germ-free mice (n=12).
Results: Older adults with high MT possessed significantly greater proportions of memory, senescent and regulatory T cells, but fewer thymic naïve T cell emigrants compared to young and old adults with low MT. Further, intestinal barrier dysfunction was associated with defective autophagy/mitophagy and reduced DNA damage repair in circulating immune cells, possibly contributing towards low immunological age (IMM-AGE) scores observed in old participants with high MT. Moreover, aged germ-free mice that maintain intestinal barrier function are protected from key features of thymic involution (such as lipid deposition and architectural disorganisation) compared to aged wild type mice.
Conclusion: These results suggest that age-associated intestinal barrier disruption and microbial translocation contribute towards thymic involution and T cell ageing. Therefore, the maintenance and restoration of intestinal barrier integrity could serve as a potential strategy for combating immune ageing and preventing morbidity.
| Period | 6 Dec 2022 |
|---|---|
| Held at | British Society of Immunology 2022 Congress, United Kingdom |
| Degree of Recognition | National |
Keywords
- Microbial translocation
- Gut permeability
- Intestinal barrier dysfunction
- Microbiota
- Microbiome
- T cell ageing
- Immunesenescence
- Ageing