This study uses single-cell RNA sequencing to analyze facial skin from female rosacea patients and healthy individuals. A keratinocyte subpopulation with IFNγ-mediated barrier damage is unique to rosacea. Blocking IFNγ signaling improves rosacea-like phenotypes in mice. Papulopustular rosacea shows increased pro-inflammatory fibroblasts, Schwann cells, endothelial cells, and macrophages/dendritic cells. Fibroblasts are identified as the primary source of pro-inflammatory and vasodilative signals. Fibroblast depletion or PTGDS knockdown prevents rosacea development in mice. The study comprehensively details aberrant skin-resident cell populations and highlights fibroblasts as a key determinant in rosacea.

Mengting Chen, Li Yang, Peijie Zhou, Suoqin Jin, Zheng Wu, Zixin Tan, Wenqin Xiao, San Xu, Yan Zhu, Mei Wang, Dan Jian, Fangfen Liu, Yan Tang, Zhixiang Zhao, Yingxue Huang, Wei Shi, Hongfu Xie, Qing Nie, Ben Wang, Zhili Deng, Ji Li