
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.10.612119
preprint
1
Article
Longitudinal Multi-omic Immune Profiling Reveals Age-Related Immune Cell Dynamics in Healthy Adults
Gong Qiuyu http://orcid.org/0009-0006-3885-0862

Sharma Mehul http://orcid.org/0000-0002-9591-0415

Kuan Emma L. http://orcid.org/0000-0002-5824-2016

Glass Marla C. http://orcid.org/0000-0003-3763-0842

Chander Aishwarya http://orcid.org/0000-0002-0459-7583

Singh Mansi http://orcid.org/0009-0004-7045-1410

Graybuck Lucas T. http://orcid.org/0000-0002-8814-6818

Thomson Zachary J. http://orcid.org/0000-0002-3861-9998

LaFrance Christian M. http://orcid.org/0009-0006-0763-2002

Zaim Samir Rachid http://orcid.org/0009-0007-9256-2324

Peng Tao http://orcid.org/0000-0003-0550-9183

Okada Lauren Y. http://orcid.org/0000-0002-5691-3373

Genge Palak C http://orcid.org/0000-0002-0851-6445

Henderson Katherine E. http://orcid.org/0000-0001-8682-5051

Dornisch Elisabeth M. http://orcid.org/0009-0009-6969-8690

Layton Erik D. http://orcid.org/0000-0001-6409-290X

Wittig Peter J. http://orcid.org/0009-0000-9639-5518

Heubeck Alexander T. http://orcid.org/0000-0002-9312-4090

Mukuka Nelson M. http://orcid.org/0009-0005-9579-8389

Reading Julian http://orcid.org/0000-0002-8533-3992

Roll Charles R. http://orcid.org/0000-0002-0726-2076

Hernandez Veronica http://orcid.org/0000-0003-2568-2565

Parthasarathy Vaishnavi http://orcid.org/0009-0007-0090-5861

Stuckey Tyanna J. http://orcid.org/0009-0003-3262-8441

Musgrove Blessing http://orcid.org/0009-0000-0640-723X

Swanson Elliott http://orcid.org/0000-0002-0351-6446

Lord Cara http://orcid.org/0000-0002-7827-2159

Weiss Morgan D.A. http://orcid.org/0000-0002-4189-1992

Phalen Cole G. http://orcid.org/0000-0002-0196-2805

Mettey Regina R.
Lee Kevin J. http://orcid.org/0009-0001-9539-764X

Johanneson John B. http://orcid.org/0009-0002-7612-1290

Kawelo Erin K. http://orcid.org/0009-0004-0329-9914

Garber Jessica http://orcid.org/0009-0007-8773-9754

Krishnan Upaasana http://orcid.org/0000-0001-8589-7061

Smithmyer Megan http://orcid.org/0000-0002-1005-0621

Wherry E. John http://orcid.org/0000-0003-0477-1956

Vella Laura http://orcid.org/0000-0002-8917-4845

Henrickson Sarah E. http://orcid.org/0000-0001-5569-4132

Kopp Mackenzie S. http://orcid.org/0000-0002-7436-5622

Savage Adam K. http://orcid.org/0000-0003-1913-5485

Becker Lynne A. http://orcid.org/0000-0003-1541-4655

Meijer Paul http://orcid.org/0000-0001-5535-0399

Coffey Ernest M. http://orcid.org/0009-0001-4596-0246

Goronzy Jorg J. http://orcid.org/0000-0001-7670-1856

Speake Cate http://orcid.org/0000-0003-1480-4272

Bumol Thomas F. http://orcid.org/0000-0003-4319-1006

Goldrath Ananda W. http://orcid.org/0000-0002-5900-508X

Torgerson Troy R. http://orcid.org/0000-0003-3489-5036

Li Xiao-jun http://orcid.org/0000-0003-0832-9479

Skene Peter J. http://orcid.org/0000-0001-8965-5326

Buckner Jane H. http://orcid.org/0000-0002-9005-1885

Gustafson Claire E. http://orcid.org/0000-0002-1437-6709

14 9 2024
2024.09.10.612119https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.10.612119
nihpp-2024.09.10.612119.pdf
Summary

The generation and maintenance of protective immunity is a dynamic interplay between host and environment that is impacted by age. Understanding fundamental changes in the healthy immune system that occur over a lifespan is critical in developing interventions for age-related susceptibility to infections and diseases. Here, we use multi-omic profiling (scRNA-seq, proteomics, flow cytometry) to examined human peripheral immunity in over 300 healthy adults, with 96 young and older adults followed over two years with yearly vaccination. The resulting resource includes scRNA-seq datasets of >16 million PBMCs, interrogating 71 immune cell subsets from our new Immune Health Atlas. This study allows unique insights into the composition and transcriptional state of immune cells at homeostasis, with vaccine perturbation, and across age. We find that T cells specifically accumulate age-related transcriptional changes more than other immune cells, independent from inflammation and chronic perturbation. Moreover, impaired memory B cell responses to vaccination are linked to a Th2-like state shift in older adults’ memory CD4 T cells, revealing possible mechanisms of immune dysregulation during healthy human aging. This extensive resource is provided with a suite of exploration tools at https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/ to enhance data accessibility and further the understanding of immune health across age.
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