32823 Single-cell transcriptomic analysis of cutaneous T cells in psoriasis

Abstract

Psoriasis is an immune-mediated disease characterized by skin and systemic inflammation that affects 125 million people worldwide. However, the underlying pathways contributing to psoriasis pathogenesis have not been fully elucidated. This project uses single-cell transcriptomes of T cells and other immune cell types from healthy and psoriatic skin in an effort to identify key biomarkers and pathways of psoriasis. T cells were clustered into subtypes and differential gene expression analysis was performed between lesional and healthy skin to identify psoriatic marker genes in each T cell subtype. Regulatory CD4+ T cells in psoriasis lesional skin were found to upregulate cytokines such as IL-32, as well as genes in the interferon-gamma-mediated signaling, NF-κB signaling, and putrescine catabolic pathways. As a result, psoriatic Tregs may amplify several of the pathways behind psoriasis and drive inflammation via IL-32, which has been previously found to be significantly upregulated in plaque psoriasis. Ongoing work includes using stratification by HLA type, VDJ analysis to more closely investigate psoriatic TCR abnormalities, and incorporation of more patient data.