Age-Specific Immune Signatures Identified Across the Atopic Dermatitis Lifespan

A single-cell multi-omics analysis has identified distinct age-related immune and molecular programs in atopic dermatitis (AD), suggesting that pediatric, adult, and geriatric disease may represent biologically distinct subtypes built upon a shared Th2 inflammatory foundation.

Researchers analyzed peripheral blood mononuclear cells from 29 patients with AD and 29 matched healthy controls spanning pediatric, adult, and geriatric age groups. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing, investigators simultaneously assessed transcriptomic and surface proteomic profiles across approximately 280,000 immune cells.

Compared with healthy controls, patients with AD demonstrated enrichment of CD14+ monocytes, plasmacytoid dendritic cells, and CD4+ proliferating T cells. Differential expression analyses also identified Th2-associated inflammatory signatures that were shared across all age groups.

However, substantial age-dependent differences emerged. Pediatric patients exhibited increased γδ T cells, as well as naïve CD4+ and CD8+ T-cell populations. In contrast, geriatric patients demonstrated increased CD4+ cytotoxic T cells and CD8+ central memory T cells, suggesting a shift from naïve to effector immune cell predominance with aging.

Distinct molecular pathways also characterized each age group. Pediatric AD was associated with enrichment of IL-10 and cytokine-cytokine receptor signaling pathways. Adult AD showed activation of metabolic pathways and nuclear factor kappa-light-chain-enhancer of activated B cells, Th1, and Th17 signaling. Geriatric AD was characterized by reduced adaptive immune activity alongside increased innate immune signaling.

Machine-learning analyses further supported biologic distinctions among age groups. Models based on differentially expressed genes and proteins accurately classified AD subgroups, achieving a transcript-based F1 score of 0.70 and an area under the curve of 0.79. Stable markers included IRF2, PDK4, ZFP90, CD21, CD94, and CD122.

According to the investigators, “single-cell multi-omics profiling revealed age-specific transcriptional and immunological programs overlaid on a shared Th2-driven inflammatory foundation in AD.” The authors further noted that “rather than discrete disease states,” pediatric, adult, and geriatric AD demonstrated distinct developmental, inflammatory, and metabolic signatures.

Reference
Baldonado GCL, Kumar S, Jin J, et al. Immunological differences in atopic dermatitis across age groups: insights from single-cell multi-omics. J Transl Med. Published online June 1, 2026. doi:10.1186/s12967-026-08288-7