A multi-organ map of the human immune system across age, sex and ethnicity.

S Mangiola, M Milton, N Ranathunga, Csn Li-Wai-Suen, A Odainic, E Yang, W Hutchison, A Garnham, J Iskander, B Pal, V Yadav, Jfj Rossello, V J Carey, M Morgan, S Bedoui, A Kallies,A T Papenfuss

bioRxiv : the preprint server for biology(2024)

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Abstract
Understanding tissue biology's heterogeneity is crucial for advancing precision medicine. Despite the centrality of the immune system in tissue homeostasis, a detailed and comprehensive map of immune cell distribution and interactions across human tissues and demographics remains elusive. To fill this gap, we harmonised data from 12,981 single-cell RNA sequencing samples and curated 29 million cells from 45 anatomical sites to create a comprehensive compositional and transcriptional healthy map of the healthy immune system. We used this resource and a novel multilevel modelling approach to track immune ageing and test differences across sex and ethnicity. We uncovered conserved and tissue-specific immune-ageing programs, resolved sex-dependent differential ageing and identified ethnic diversity in clinically critical immune checkpoints. This study provides a quantitative baseline of the immune system, facilitating advances in precision medicine. By sharing our immune map, we hope to catalyse further breakthroughs in cancer, infectious disease, immunology and precision medicine.
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