| Aging systemic T cells have attracted attention as potential therapeutic targets in aging. However, there are few reports on the aging of the intestinal immune system, which differs from the systemic immune system in many ways. Therefore, we investigated the age-related changes in the intestinal immune system, particularly in T cells. The most significant changes were observed in IEL CD4, with an increased proportion of CD27-CD28-, characteristic of ageing T cells, and an increased proportion of CD8a, characteristic of IELs. Their proliferative capacity was markedly reduced and transcriptome analysis showed that cytotoxic markers such as granzymeA and NK receptors were upregulated. Functional analysis showed that aging IEL T cells had a higher cytotoxic function against intestinal tumor organoids in vitro than young IEL T cells. scRNAseq revealed that two distinct unique subsets were increased in ageing IEL CD4+, that were distinct from systemic T cells. Subset 1 has a pro-inflammatory component, with expression of Ifng and upregulation of NFkB signaling pathways. Subset 2 upregulates inhibitory molecules and natural IEL markers. These fractions had different TCR repertoires. They may be involved in the suppression of intestinal aging and longevity through anti-tumor immunity, elimination of senescent cells and stressed cells in the aging environment. This finding could be a breakthrough in aging research. |
