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Presentation

Single-Cell and Spatial Transcriptomics Reveal Site-Specific Immune Programs in Healthy Skin and Inflammatory Disease

Description

The talk described how single-cell and spatial transcriptomics are transforming our understanding of skin by revealing that different body sites harbor distinct cellular ecosystems and baseline immune programs. The speaker reviewed the historical progression from early anatomical descriptions to modern omics approaches, then showed that skin varies by location in hair follicle density, innervation, vascularization, microbiome exposure, and mechanical stress, all of which shape site-specific transcriptional states and disease susceptibility. Using biopsies from multiple anatomic sites, the team found that major cell types, including keratinocytes, fibroblasts, immune cells, endothelial cells, and Schwann cells, differ in proportion across the body, with especially notable immune differences in facial skin, which shows signs of low-grade inflammation even when healthy. They also highlighted T-cell heterogeneity in normal skin, including CD4, CD8, Treg, NK-like, and innate lymphoid populations, and showed that these subsets are unevenly distributed across sites. In disease, especially atopic dermatitis, the data revealed increased T-cell infiltration and site-specific expression of the OX40/OX40L axis, including expression on Tregs, suggesting a mechanism that can weaken suppressive function and promote inflammation. Overall, the presentation argued that tissue context shapes how shared immune pathways manifest across skin sites and that spatially resolved immune mapping will enable more precise dermatologic diagnosis and therapy.

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Conclusions

Normal skin is not immunologically uniform; it contains distinct, site-specific cellular ecosystems with different baseline immune programs across body regions.
Local factors such as hair density, sweat glands, UV exposure, friction, microbiome, and vascularity shape the skin’s transcriptional and immune landscape.
Single-cell and spatial transcriptomics reveal that major skin cell types and immune subsets are distributed very differently by anatomic site.
Healthy skin already contains diverse T-cell and myeloid populations, but their proportions vary substantially depending on location.
Facial skin appears to show a relatively higher low-grade inflammatory immune tone than many other sites, possibly reflecting constant environmental stress.
Cell-cell communication between immune cells and skin structures is site dependent, meaning tissue context strongly influences how immune responses are organized.
The OX40/OX40L pathway is expressed differently across skin sites and appears to be especially relevant to inflammatory signaling in atopic dermatitis.
Atopic dermatitis is associated with expansion of T cells and increased TNFRSF4/OX40 expression, including on T-regulatory cell populations, which may weaken suppressive control and promote inflammation.
Disease manifestation is shaped by tissue context, so shared immune pathways can produce different clinical patterns depending on where in the skin they occur.
These findings support a precision dermatology approach in which therapy is guided not only by which pathway is active, but also by which skin compartment and anatomic site are involved.

Gudjonsson JE, et al. From Skin Homeostasis to Autoimmunity: How Normal Immune Programs Become Pathogenic. AAD 2026.
Disease relevance of TNFRSF4 (OX40-R).
TNFRSF4 expression in healthy scalp T cells is amplified in atopic dermatitis.
U085. Immune (Dys)regulation in Autoimmune Skin Diseases.