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Peer-reviewedCC BY-NC-NDNature Communications

Single-cell map of the healthy human immune system across the lifespan reveals unique infant immune signatures

  • Djamel Nehar-Belaid1,2
  • Asa Thibodeau3,2
  • Alper Eroğlu4,5,3,6,7,8,2
  • Radu Marcheş3,2
  • Giray Naim Eryilmaz3,2
  • Titas Grabauskas3,2
  • Luke Trinity3,9,10,11,12,13
  • Derya Unutmaz3,14
  • Chris P. Verschoor15,16,14
  • Jinghua Gu17,18
  • Uthra Balaji17,14
  • Asunción Mejías19,20
5 more authors
  • Virginia Pascual17,18
  • George A. Kuchel20,21,2
  • Octavio Ramilo19,22,2
  • Jacques Banchereau21,3
  • Duygu Ucar23,24
24 affiliations
  1. 1The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. [email protected]
  2. 2The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032 USA
  3. 3The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
  4. 4Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden
  5. 5SciLifeLab, Stockholm, Sweden
  6. 6Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, 171 77, Sweden
  7. 7SciLifeLab
  8. 8Solna, Stockholm, 171 65, Sweden
  9. 9Department of Medicine, McMaster University
  10. 10Hamilton, ON L8S 4L8 Canada
  11. 11Health Sciences North Research Institute
  12. 12NOSM University
  13. 13Sudbury, ON P3E 2H3, Canada
  14. 14Drukier Institute for Children's Health and Department of Pediatrics, Weill Cornell Medicine, New York, NY
  15. 15Department of Medicine, McMaster University, Hamilton, ON, Canada
  16. 16Health Sciences North Research Institute, NOSM University, Sudbury, ON, Canada
  17. 17Drukier Institute for Children's Health and Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA
  18. 18Department of Infectious Diseases, St. Jude Children's Research Hospital, 22 Danny Thomas Place, Memphis, TN 38105
  19. 19Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA
  20. 20UConn Center on Aging, University of Connecticut, Farmington, CT, USA
  21. 21Immunoledge LLC, Montclair, NJ, USA
  22. 22Institute for Systems Genomics, University of Connecticut Health Center, Farmington, CT, USA
  23. 23Institute for Systems Genomics, University of Connecticut Health Center, Farmington, CT, USA. [email protected]
  24. 24The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. [email protected]
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Abstract

The human immune system undergoes continuous remodeling from infancy through old age, yet the timing and trajectory of these changes across the lifespan remain poorly defined. To address this, we profiled peripheral blood mononuclear cells from 95 healthy individuals (ages 2 months to 88 years), including infants (n=27), children (n=23), adults (n=18), and older adults (n=27) using scRNA-seq and snATAC-seq. MAIT and γδ T cells showed a “Rise and fall” pattern, which rise in childhood, peak in young adulthood, and decline with age. CD8 + T cells were the most affected by aging with decreasing naïve T cells and increasing GzK + CD8 + T cells and TEMRA cells. Infants had lower myeloid/lymphoid ratio, with a distinct composition marked by increased frequencies of CD16 + monocytes and plasmacytoid dendritic cells and reduced frequencies of CD14 + monocytes and conventional DCs. Their adaptive immune compartment also displayed unique features, including constitutive interferon-stimulated gene expression in T and B cells, and an expanded SOX4 + populations in naïve CD4 + , naïve CD8 + and γδ T cells, comprising ∼30% of the naïve T cell pool. SOX4 + naïve CD4 + T cells displayed a Th2 epigenetic signature. This map provides critical insights into human immune system dynamics across the lifespan, emphasizing unique features of the infant immune system.

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Cite

BibTeXRIS
BibTeX
@article{neharbelaid2026singlecell,
  title = {{Single-cell map of the healthy human immune system across the lifespan reveals unique infant immune signatures}},
  author = {Djamel Nehar-Belaid and Asa Thibodeau and Alper Eroğlu and Radu Marcheş and Giray Naim Eryilmaz and Titas Grabauskas and Luke Trinity and Derya Unutmaz and Chris P. Verschoor and Jinghua Gu and Uthra Balaji and Asunción Mejías and Virginia Pascual and George A. Kuchel and Octavio Ramilo and Jacques Banchereau and Duygu Ucar},
  journal = {Nature Communications},
  year = {2026},
  month = jun,
  doi = {10.1038/s41467-026-73729-2},
  url = {https://doi.org/10.1038/s41467-026-73729-2},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Single-cell map of the healthy human immune system across the lifespan reveals unique infant immune signatures
AU  - Djamel Nehar-Belaid
AU  - Asa Thibodeau
AU  - Alper Eroğlu
AU  - Radu Marcheş
AU  - Giray Naim Eryilmaz
AU  - Titas Grabauskas
AU  - Luke Trinity
AU  - Derya Unutmaz
AU  - Chris P. Verschoor
AU  - Jinghua Gu
AU  - Uthra Balaji
AU  - Asunción Mejías
AU  - Virginia Pascual
AU  - George A. Kuchel
AU  - Octavio Ramilo
AU  - Jacques Banchereau
AU  - Duygu Ucar
PY  - 2026
DA  - 2026/06/15
JO  - Nature Communications
DO  - 10.1038/s41467-026-73729-2
UR  - https://doi.org/10.1038/s41467-026-73729-2
AB  - The human immune system undergoes continuous remodeling from infancy through old age, yet the timing and trajectory of these changes across the lifespan remain poorly defined. To address this, we profiled peripheral blood mononuclear cells from 95 healthy individuals (ages 2 months to 88 years), including infants (n=27), children (n=23), adults (n=18), and older adults (n=27) using scRNA-seq and snATAC-seq. MAIT and γδ T cells showed a “Rise and fall” pattern, which rise in childhood, peak in young adulthood, and decline with age. CD8 + T cells were the most affected by aging with decreasing naïve T cells and increasing GzK + CD8 + T cells and TEMRA cells. Infants had lower myeloid/lymphoid ratio, with a distinct composition marked by increased frequencies of CD16 + monocytes and plasmacytoid dendritic cells and reduced frequencies of CD14 + monocytes and conventional DCs. Their adaptive immune compartment also displayed unique features, including constitutive interferon-stimulated gene expression in T and B cells, and an expanded SOX4 + populations in naïve CD4 + , naïve CD8 + and γδ T cells, comprising ∼30% of the naïve T cell pool. SOX4 + naïve CD4 + T cells displayed a Th2 epigenetic signature. This map provides critical insights into human immune system dynamics across the lifespan, emphasizing unique features of the infant immune system.
SN  - 2041-1723
ER  -