{"title":"Keratinocytes: new perspectives in inflammatory skin diseases.","authors":"Jiafeng Ye, Yuping Lai","doi":"10.1016/j.molmed.2025.03.012","DOIUrl":null,"url":null,"abstract":"<p><p>Keratinocytes, the predominant cell type in the epidermis, are indispensable for maintaining skin barrier integrity, mediating host defense, and orchestrating immune responses. Beyond these well-established functions, emerging evidence reveals their dynamic interactions with the nervous system and their capacity to retain inflammatory memory. These discoveries position keratinocytes as key drivers of the onset, progression, and relapse of inflammatory skin diseases. In this review, we delve into the mechanisms underlying keratinocyte crosstalk with immune and neural cells, the metabolic reprogramming, including lactate and other metabolites, that may drive inflammatory memory, and the broader implications for disease pathogenesis and recurrence. Finally, we discuss the challenges to, and therapeutic potential of, targeting keratinocytes for the treatment of chronic inflammatory skin conditions.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8000,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in molecular medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.molmed.2025.03.012","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Keratinocytes, the predominant cell type in the epidermis, are indispensable for maintaining skin barrier integrity, mediating host defense, and orchestrating immune responses. Beyond these well-established functions, emerging evidence reveals their dynamic interactions with the nervous system and their capacity to retain inflammatory memory. These discoveries position keratinocytes as key drivers of the onset, progression, and relapse of inflammatory skin diseases. In this review, we delve into the mechanisms underlying keratinocyte crosstalk with immune and neural cells, the metabolic reprogramming, including lactate and other metabolites, that may drive inflammatory memory, and the broader implications for disease pathogenesis and recurrence. Finally, we discuss the challenges to, and therapeutic potential of, targeting keratinocytes for the treatment of chronic inflammatory skin conditions.
期刊介绍：
Trends in Molecular Medicine (TMM) aims to offer concise and contextualized perspectives on the latest research advancing biomedical science toward better diagnosis, treatment, and prevention of human diseases. It focuses on research at the intersection of basic biology and clinical research, covering new concepts in human biology and pathology with clear implications for diagnostics and therapy. TMM reviews bridge the gap between bench and bedside, discussing research from preclinical studies to patient-enrolled trials. The major themes include disease mechanisms, tools and technologies, diagnostics, and therapeutics, with a preference for articles relevant to multiple themes. TMM serves as a platform for discussion, pushing traditional boundaries and fostering collaboration between scientists and clinicians. The journal seeks to publish provocative and authoritative articles that are also accessible to a broad audience, inspiring new directions in molecular medicine to enhance human health.
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