Immune Dynamics in Palmoplantar Pustulosis Unveiled by Single-Cell and High-Resolution Spatial Transcriptomics [scRNA-seq]

In this study, we mapped the immune landscape underlying PPP progression using single-cell RNA sequencing (scRNA-seq) integrated with high-resolution spatial transcriptomics (ST). Keratinocytes and fibroblasts in PPP showed enhanced activation of the JAK–STAT signaling pathway, alongside a progressive accumulation of myeloid dendritic cells and Th17 cells across disease stages—from healthy control (HC) to non-pustular lesion (NPL), and then to pustular lesion (PL).

Cell–cell interaction analysis revealed CCL19–CCR7 signaling between fibroblastic reticular cell (FRC)-like fibroblasts and LAMP3⁺/CCR7⁺ migratory dendritic cells, as well as CCL22/CCL17–CCR4 signaling between these dendritic cells and CD4⁺ T cells, including Th17 subsets. These interactions were spatially validated, with dendritic cells localized both within pustules and in the upper dermis. Within the CCL19⁺ dermal compartment, activated antigen-presenting cells and lymphocytes coalesced into a lymphoid-like immune structure.