Immunological Differences in Atopic Dermatitis Across Age Groups: Insights from Single-Cell Multi-Omics.

Area of Science:

• Immunology
• Genomics
• Dermatology
• Computational Biology

Background:

• Atopic dermatitis (AD) presents with varied clinical and immunological features in children, adults, and older adults.
• The molecular underpinnings of these age-specific immune variations in AD are not well understood.

Purpose of the Study:

• To investigate the age-specific immune system differences in atopic dermatitis (AD) patients.
• To identify molecular signatures associated with AD across different age groups using single-cell multi-omics.

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 (HC) across pediatric, adult, and geriatric groups.
• Simultaneous quantification of transcriptomic (RNA) and surface proteomic (ADT) profiles.
• Machine-learning classifiers were developed to distinguish AD subgroups based on identified gene and protein features.

Main Results:

• AD blood samples showed increased CD14+ monocytes, plasmacytoid dendritic cells, and CD4+ proliferating T cells compared to HC.
• Pediatric AD featured higher γδ T cells and naïve T cells, while geriatric AD showed more CD4+ cytotoxic and CD8+ central memory T cells.
• Distinct molecular pathways were identified: pediatric AD (IL-10 signaling), adult AD (NF-κB/Th1/Th17 pathways), and geriatric AD (enhanced innate signaling).

Conclusions:

• Single-cell multi-omics reveals age-dependent immune system shifts in atopic dermatitis, from developmental tolerance in children to inflammatory and innate signaling dominance in older adults.
• Identified molecular signatures and stable biomarkers can potentially guide the development of age-specific diagnostic and therapeutic strategies for AD across the lifespan.