{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE341nnn/GSE341985/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE341985"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Diseaase context dictates the cellular targets of IL-17 in inflammatory skin disease [2]","description":"Therapeutic blockade of IL-17 and TNF can effectively treat inflammatory skin diseases such as hidradenitis suppurativa and psoriasis, yet the relative importance of the different cell types that respond to IL-17 and TNF remains unresolved. Keratinocytes are viewed as the dominant effector cells, whereas fibroblasts have recently emerged as important contributors. In mice, topical imiquimod induces IL-17- and TNF-dependent skin inflammation and is frequently used to model psoriasis. Here, we demonstrate that intradermal injection of recombinant IL-17 and TNF elicits skin inflammation with features of hidradenitis suppurativa, including a gene expression program that is distinct from psoriasis and imiquimod-induced inflammation. Single-cell transcriptomic network analysis identified dermal fibroblasts as the dominant cell communication hub in hidradenitis suppurativa and in mice injected with IL-17 and TNF. In contrast, fibroblasts and keratinocytes both show strong network involvement in psoriasis and in mice challenged with imiquimod. Cell-type-specific deletion of IL-17 receptor A in mice revealed that imiquimod-induced inflammation depends equally on IL-17 signaling in fibroblasts and keratinocytes, whereas inflammation induced by intradermal IL-17 and TNF only requires fibroblasts to recognize IL-17 and is independent of keratinocyte IL-17 sensing. Single-cell transcriptomic analysis of these conditional knockout mice further demonstrated that keratinocytes and fibroblasts activate divergent and disease-dependent transcriptional programs following activation by IL-17. Together, these findings introduce a new conceptual framework wherein IL-17 signaling is routed through distinct cellular and molecular pathways depending on disease context and establish complementary experimental systems for interrogating type 17 skin inflammation.","dates":{"publication":"2026/08/07"},"accession":"GSE341985","cross_references":{"GSM":["GSM9921362","GSM9921361","GSM9921360","GSM9921369","GSM9921368","GSM9921367","GSM9921366","GSM9921365","GSM9921364","GSM9921363","GSM9921351","GSM9921373","GSM9921372","GSM9921350","GSM9921371","GSM9921370","GSM9921359","GSM9921358","GSM9921357","GSM9921356","GSM9921355","GSM9921354","GSM9921376","GSM9921375","GSM9921353","GSM9921374","GSM9921352"],"GPL":["24247"],"GSE":["341985"],"taxon":["Mus musculus"]}}