Comparison of Keratinocyte and Myeloid Transcriptional Phenotypes and Shared Candidate Features Between Acute Irritant and Allergic Contact Dermatitis Based on Single-Cell RNA Sequencing

Abstract

 This study compared the transcriptional phenotypes of keratinocytes (KCs) and the myeloid compartment after exposure in acute irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD), and identified candidate shared features. This study is a secondary analysis of public single-cell RNA sequencing data. We analyzed GEO dataset GSE267929, focusing on healthy individuals and squaric acid dibutyl ester (SADBE)-sensitized volunteers; in the latter group, sodium lauryl sulfate (SLS) induced ICD and SADBE induced ACD. Samples included vehicle, non-lesional, and healthy control groups. After quality control (including doublet removal and ambient-RNA correction) and annotation with Seurat v5, we performed pseudobulk differential expression, subject-blocked enrichment, program scoring, CellChat, and Milo analyses. A total of 43,303 cells were assigned to 14 populations/states, and 1,727 cells were recovered from ICD samples.  KC stress/injury markers were consistently increased in ICD donors (an ICD-predominant phenotype rather than a shared feature): stress keratins were upregulated in all 5 paired donors, and MIF was upregulated in all 6 evaluable donors; KRT6A, MIF, and S100A7 had nominal P < 0.05 (nominal P refers to the raw P value without multiple-comparison correction and is exploratory). Here, MIF is produced by KCs and does not originate solely from macrophages.   The IL-8/neutrophil program was upregulated and enriched in both KCs and myeloid cells on Day 2 after patch application in ICD and ACD, but did not reach significance on Day 4 in ACD (Day 2 refers to 2 days after patch application; Day 4 refers to patch application for 2 days, removal, and observation for another 2 days); no formal time-interaction test was performed, so this cannot be described as a decrease over time.    CXCL8 and MMP12 were identified as hypothesis-generating shared candidate molecules for further validation. In this study, “shared” operationally means that both diseases show upregulation relative to non-lesional skin, rather than formal equivalence or interaction testing. The molecular initiation, the temporal order of the KC→myeloid axis, and common downstream effects remain undetermined, and the results cannot be extrapolated to unsensitized populations or chronic dermatitis.