{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:36:14Z","timestamp":1792794974372,"version":"4.5.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by epidermal dysfunction, aberrant keratinocyte activation, and complex immune remodeling. Although lipid dysregulation has increasingly been implicated in psoriasis, the role of palmitoylation-associated genes in cutaneous inflammation remains insufficiently defined.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We integrated bulk transcriptomic datasets (GSE14905, GSE13355, and GSE121212) and a single-cell RNA-sequencing dataset (GSE151177) to identify palmitoylation-associated biomarkers in psoriasis. Weighted gene co-expression network analysis, differential expression analysis, and machine-learning algorithms including LASSO and SVM-RFE were applied to screen hub genes. Functional enrichment, immune microenvironment analysis, regulatory-network construction, and candidate-drug prediction were subsequently performed. In addition, RT-qPCR was used to validate the expression of candidate genes in psoriatic lesional skin and healthy control skin.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We identified 209 palmitoylation-associated differentially expressed genes and screened five candidate hub genes:\n CERK<\/jats:italic>\n ,\n SPTSSA<\/jats:italic>\n ,\n TNFSF10<\/jats:italic>\n ,\n CTNS<\/jats:italic>\n , and\n HSD17B10<\/jats:italic>\n . External validation supported the relative robustness of\n SPTSSA<\/jats:italic>\n ,\n TNFSF10<\/jats:italic>\n , CTNS, and\n HSD17B10<\/jats:italic>\n , whereas\n CERK<\/jats:italic>\n remained a biologically relevant mechanistic candidate. A four-gene score derived from\n SPTSSA<\/jats:italic>\n ,\n TNFSF10<\/jats:italic>\n , CTNS, and\n HSD17B10<\/jats:italic>\n defined a high-score state enriched in inflammatory, proliferative, and metabolic-stress pathways, including interferon responses, IL-6\u2013JAK\u2013STAT3 signaling, TNF signaling via NF-\u03baB, complement, and inflammatory response. Immune deconvolution further revealed increased macrophage and activated dendritic-cell infiltration together with coordinated upregulation of multiple immune checkpoint molecules. Single-cell and correlation analyses suggested that\n SPTSSA<\/jats:italic>\n showed relatively stronger expression in basal cells and keratinocytes, supporting a closer association with epidermal programs.\n CTNS<\/jats:italic>\n also exhibited a mainly epidermal distribution, particularly in keratinocytes, whereas\n TNFSF10<\/jats:italic>\n displayed a more immune-related pattern and\n HSD17B10<\/jats:italic>\n showed a broader immune-metabolic distribution across multiple cell populations. RT-qPCR further supported the lesional upregulation of\n SPTSSA<\/jats:italic>\n and\n HSD17B10<\/jats:italic>\n , while\n CERK<\/jats:italic>\n showed an opposite tissue-level trend and was therefore retained as a mechanistically informative candidate.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This study identifies a palmitoylation-associated molecular signature related with sphingolipid metabolism, keratinocyte activation, and immune remodeling in psoriasis. These findings not only provide candidate biomarkers for disease stratification, but also highlight potentially druggable pathways and therapeutic targets for future translational investigation.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1856647","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:20:13Z","timestamp":1784607613000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated transcriptomic and tissue-validation analyses identify palmitoylation-associated biomarkers linked to sphingolipid metabolism and immune remodeling in psoriasis"],"prefix":"10.3389","volume":"17","author":[{"given":"Qingqiong","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University","place":["Shanghai, 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