FC02 Immune cell signatures and T-cell receptor profiling reveal pathogenetic mechanisms in psoriasis

Abstract Psoriasis is a chronic inflammatory disease with systemic effects and currently has no cure due to an incomplete understanding of its underlying mechanisms. To gain better insights into the immune response associated with psoriasis, we conducted single-cell RNA sequencing and parallel single-cell T-cell receptor (TCR) profiling on peripheral blood mononuclear cells obtained from 11 psoriasis patients and 8 healthy controls. Additionally, we analysed two pairs of skin samples from the psoriasis cohort and performed spatial transcriptomics on two other pairs of skin samples. Our study identified specific immune signatures in myeloid and lymphocyte subsets both in blood and skin and highlighted characteristics of the immune repertoire in psoriasis. Notably, we found an increased proportion of circulating CD14+ monocytes. Furthermore, circulating plasmacytoid dendritic cells in psoriasis patients exhibited heightened expression of genes associated with skin-homing and pro-inflammatory responses. Circulating T cells in these patients showed decreased expression of activation markers. In psoriatic lesions, we observed that resting CD8+ tissue-resident memory T (TRM) cells displayed a gene expression profile similar to that of activated CD8+ TRM cells, though they had lower expression levels of cytotoxicity-related genes. Both resting and activated CD8+ TRM cells in psoriatic lesions showed enhanced interaction strength in terms of signal transmission and reception compared with non-lesions. Activated CD8+ TRM cells were densely infiltrated in the dermis of skin lesions, while resting CD8+ TRM cells were located deeper in the dermis of non-lesion areas. TCR clones that were highly expanded in skin lesions were predominantly CD8+ TRM cells. Distinct TCR clusters showed different gene expression signatures, with one CD8+ TRM cluster expressing IFNγ and another expressing IL-17. These findings provide a valuable resource for further investigation into the pathogenesis of psoriasis by offering insights into the immune cell dynamics within both circulation and local skin environments.