Female specific erosion of allelic fidelity in aged CD8 memory T cells
The molecular mechanisms by which sex and age remodel the mammalian immune system remain poorly understood. Here, we show at single-allele and single-cell resolution that the inactive X chromosome (Xi) is subject to cell-type-specific erosion of its transcriptional fidelity with ageing. Single-cell multiomics analysis in mice revealed this phenotype to be concentrated in aged CD8 memory T cells,…
Recent research has uncovered a female-specific erosion of allelic fidelity in aged CD8 memory T cells. The molecular mechanisms behind the changes in the mammalian immune system due to sex and age are still not fully understood. In this study, researchers examined the inactive X chromosome (Xi) at single-allele and single-cell resolution.
They discovered that the erosion of transcriptional fidelity in the Xi is greater in aged CD8 memory T cells. This phenomenon is primarily observed in aged female mice, where a higher level of Xi transcription and chromatin accessibility is coupled with enhanced immune activation and clonal expansion. These conditions define an effector-like CD8 memory subpopulation that is more prevalent in aged females.
The researchers also found that ageing CD8 memory T cells in humans upregulate known escape genes, indicating a conserved feature of the aging immune system. Overall, the findings suggest that cell-type-specific loss of fidelity in Xi maintenance is a female-specific mechanism contributing to immune aging.
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