347 A machine learning analysis enables demonstration that fibroblasts mediate neutrophil recruitment during type 17 skin inflammation

نویسندگان

چکیده

Neutrophil-associated skin diseases such as bacterial infection, psoriasis, and other dermatoses involve type 17 inflammation. Advancements in treatment may come from a more complete understanding of the cell types that participate pathogenesis disease. To address this, we first performed an unbiased investigation cell-cell communication during inflammation using machine learning approach with single-cell RNA sequencing (scRNA-Seq) data several different human mouse models. This network analysis revealed most to myeloid cells acne, S. aureus infection comes dermal fibroblasts, not keratinocytes. Further showed subsets fibroblasts were induced highly express chemokines host defense genes had activation state consistent response IL-17A TNFa. These immune acting visualized situ modeled primary 3T3-L1 fibroblasts. Following TNFa, cultured NF-kB signaling high expression AMPs neutrophil chemokines, validating our scRNA-Seq analysis. Conditioned media activated by TNFa robust chemotactic activity for neutrophils was dependent on CXCR2 CXCR4. determine vivo significance this deleted Il17ra specifically (PdgfraΔIl17ra). PdgfraΔIl17ramice impaired against reduced recruitment CXCR4 ligands after topical imiquimod, intradermal injection or wounding. findings show time are critical inflammatory skin. Thus, fibroblast represent novel therapeutic target diseases.

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ژورنال

عنوان ژورنال: Journal of Investigative Dermatology

سال: 2023

ISSN: ['1523-1747', '0022-202X']

DOI: https://doi.org/10.1016/j.jid.2023.03.352