Positionally distinct interferon-stimulated dermal immune-acting fibroblasts promote neutrophil recruitment in Sweet syndrome

作者：Kellen Cavagnero, Julie Albright, Fengwu Li, Edward Liu, Tatsuya Dokoshi, Rachael Bogle, Joseph Kirma, J. Michelle Kahlenberg, Allison C. Billi, Jennifer Fox, May P. Chan, Anthony Coon, Craig J. Dobry, Brian Hinds, Lam C. Tsoi, Paul W. Harms, Jóhann E. Guðjónsson, Richard L. Gallo · 发表于：Journal of Allergy and Clinical Immunology · 年份：2025 · DOI：10.1016/j.jaci.2025.05.029 · 被引用次数：5 · 研究领域：Autoimmune and Inflammatory Disorders、Autoimmune Bullous Skin Diseases、Tumors and Oncological Cases

BACKGROUND: Sweet syndrome is an inflammatory skin disease characterized by robust neutrophil infiltration into the dermis. The pathogenesis of Sweet syndrome and its distinguishing features compared to other neutrophilic dermatoses, such as pyoderma gangrenosum, remain poorly understood. OBJECTIVE: Our aim was to define the cellular and molecular landscape of the skin of patients with Sweet syndrome. METHODS: Single-nucleus and bulk transcriptomics were performed on archival clinical skin samples from patients with Sweet syndrome, patients with pyoderma gangrenosum, and healthy controls. For mechanistic validation, functional experiments were performed with primary human cells. Spatial transcriptomics with single-molecule resolution was used to map cell types to tissue location. RESULTS: A prominent interferon signature was identified in Sweet syndrome skin that was reduced in tissue samples from patients with pyoderma gangrenosum and healthy controls. This signature was observed in different subsets of cells, including fibroblasts that expressed interferon-induced genes. Functionally, this response was supported by analysis of cultured dermal fibroblasts that were observed to highly express neutrophil chemokines in response to activation by type I interferon. Furthermore, spatial transcriptomics revealed 2 positionally distinct interferon-activated fibroblast subsets: CXCL1-positive fibroblasts near neutrophil infiltrates and CXCL12-positive fibroblasts distal to these infi...