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Mapping Infant Immunity with Minimal Input: Integrative Single-Cell and Multiomic Profiling
Published on: April 3, 2026
Immunological differences in atopic dermatitis across age groups: insights from single-cell multi-omics.
Gian Carlo L Baldonado1, Sugandh Kumar2, Joy Jin2,3
1Department of Dermatology, University of California, 2340 Sutter Street, San Francisco, CA, 94115, USA. giancarlo.baldonado@ucsf.edu.
Journal of Translational Medicine
|June 3, 2026
Summary
Atopic dermatitis (AD) shows distinct molecular signatures across pediatric, adult, and geriatric populations. Understanding these age-specific immune profiles is key for developing tailored AD therapies.
Area of Science:
- Immunology
- Genomics
- Cell Biology
Background:
- Atopic dermatitis (AD) exhibits varying clinical and immunological features across different age groups, including children, adults, and older adults.
- The underlying molecular mechanisms driving these age-specific immune differences in AD are not well understood.
Purpose of the Study:
- To investigate the age-specific molecular and immunological programs in atopic dermatitis (AD) using single-cell multi-omics.
- To identify distinct molecular signatures of AD in pediatric, adult, and geriatric populations.
Main Methods:
- Single-cell multi-omics profiling (CITE-seq) was performed on peripheral blood mononuclear cells (PBMCs) from 29 AD patients and 29 healthy controls across three age groups.
- Simultaneous quantification of transcriptomic (RNA) and surface proteomic (ADT) data from approximately 280,000 immune cells.
- Machine-learning classifiers were employed to distinguish AD subgroups based on identified gene and protein features.
Main Results:
- AD blood samples showed enrichment of CD14+ monocytes, plasmacytoid dendritic cells, and CD4+ proliferating T cells compared to healthy controls.
- Shared Th2-associated signatures were observed across all age groups, with distinct molecular programs identified within each age subgroup: pediatric AD (IL-10, cytokine-cytokine receptor signaling), adult AD (metabolic, NF-κB/Th1/Th17 pathways), and geriatric AD (reduced adaptive immunity, increased innate signaling).
- Machine-learning models accurately classified AD age groups, identifying key markers like IRF2, PDK4, ZFP90, CD21, CD94, and CD122.
Conclusions:
- Single-cell multi-omics revealed age-specific immune programs in AD, superimposed on a common Th2-driven inflammatory basis.
- Pediatric, adult, and geriatric AD present unique molecular signatures: developmental/cytoskeletal (children), stress-response/chronic inflammatory (adults), and innate/metabolic (geriatric).
- These findings advocate for age-group molecular subtyping and the development of age-tailored therapeutic strategies for atopic dermatitis.
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