In Expert opinion on biological therapy
INTRODUCTION : Psoriasis (PSO) and psoriatic arthritis (PSA) represent a large burden of global inflammatory disease, but sustained treatment response and early diagnosis remain challenging. Both conditions arise from complex immune cell dysregulation. Single-cell techniques, including single-cell RNA sequencing (scRNA-seq), have revolutionized our understanding of pathogenesis by illuminating heterogeneous cell populations and their interactions.
AREAS COVERED : We discuss the transcriptional profiles and cellular interactions unique to PSO/PSA affecting T cells, myeloid cells, keratinocytes, innate lymphoid cells, and stromal cells. We also review advances, limitations, and future challenges associated with single-cell studies.
EXPERT OPINION : Following analyses of 22 single-cell studies, several themes emerged. A small subpopulation of cells can have a large impact on disease pathogenesis. Multiple cell types identified via scRNA-seq play supporting roles in PSO pathogenesis, contrary to the traditional paradigm focusing on IL-23/IL-17 signaling among dendritic cells and T cells. Immune cell states are dynamic, with psoriatic subpopulations aberrantly re-activating and differentiating into inflammatory phenotypes depending on surrounding signaling cues. Comparison of circulating immune cells with resident skin/joint cells have uncovered specific T cell clonotypes associated with disease. Finally, machine learning models demonstrate great promise in identifying biomarkers to diagnose clinically ambiguous rashes and PSA at earlier stages.
Jin Joy Q, Wu David, Spencer Riley, Elhage Kareem G, Liu Jared, Davis Mitchell, Hakimi Marwa, Kumar Sugandh, Huang Zhi-Ming, Bhutani Tina, Liao Wilson
2022-Nov-01
biologic therapy, inflammatory skin disease, psoriasis, psoriatic arthritis, single-cell RNA-sequencing, skin
