Single Cell and Spatial Sequencing Characterizes Cell Type Composition and Cell-Cell Interaction in Psoriasis

The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is still incompletely understood. Here we demonstrate, using a combination of single-cell and spatial-sequencing, that psoriatic fibroblasts, a hitherto unappreciated participant in psoriasis pathogenesis, contribute to the immune network in psoriasis through transition to a pro-inflammatory state characterized by CCL19 and CCL13. Fibroblasts interact with three other main cell-types that are in close proximity: keratinocytes, T cells and myeloid cells, that also interact with each other. In addition, our data demonstrates striking compartmentalization of inflammatory responses in distinct layers of the psoriatic epidermis, including IL-17A responses and autocrine IL-36 autoinflammatory activity within the supraspinous layer. Lastly, our data defined the T cell and myeloid populations involved in psoriasis, including enrichment of CD8+ IL17A expressing T cells, CD16+ dendritic cells, and LAMP3+ dendritic cells. These data provide an unprecedented view of psoriasis pathogenesis, which expands our understanding of the critical cellular players to include inflammatory fibroblasts as well as their cell-cell interactions, defines the spatial compartmentalization of specific inflammatory processes, together a unique resource for future investigations. Overall design: To study cell type compositon and transcription changes in normal skin from healthy donors, peripheral normal skin from psoriasis patients and psoriatic skin from psoriasis patients