Comprehensive characterization of primary ciliated cells in inflammatory skin diseases

Primary cilia are non-motile organelles that act as cellular "antennas" to sense extracellular signals. As functional studies of primary cilia across various organs and tissues have progressed, it has become clear that primary cilia are also formed in skin-resident cells, including keratinocytes. Keratinocytes maintain skin homeostasis by producing cytokines and chemokines in response to external stimuli, and supporting skin tissue homeostasis through interactions with surrounding cells. Therefore, dysregulation of keratinocyte signaling leads to the development of inflammatory skin diseases. We revealed that ciliated cells are markedly increased in atopic dermatitis (AD) and psoriasis. However, their functional roles remain unclear. We combined immunofluorescence staining and spatial transcriptomics (Visium HD), which provides single-cell-level spatial resolution within tissue sections. Immunostaining of healthy skin, AD lesions, and psoriatic skin before and after phototherapy revealed that, even after phototherapy-when epidermal thickening and inflammation were alleviated-the number of ciliated cells remained higher than in healthy skin. Transcriptomic analysis revealed that ciliated cells retained features of undifferentiated keratinocytes and exhibited upregulation of metabolic, cell-cycle, and signaling pathways compared to post-treatment cells. These findings suggest that disease-associated primary cilia may disrupt keratinocyte signaling and skin barrier maturation, and could promote disease relapse by facilitating rapid inflammatory responses upon re-stimulation. Our findings suggest that modulating cilia formation or cilia-associated signaling could provide a potential therapeutic strategy for inflammatory skin diseases.