{"id":"doi:10.1002/advs.78035","kind":"article","title":"Long-Term Human Skin Platform for Modeling Chronic Inflammation, Environmental Stress, and Therapeutic Intervention","authors":["Sharma PK","Schaafsma E","Anderson E","Chiari J","Thompson P","Galt E","Lee S","Holsapple J","Hein S","Coates BL","Michaud J","Zuccaro S","Kent L","Hinojosa C","Jang KJ"],"author_count":15,"year":2026,"published":"2026-09-29","venue":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","cited_by":0,"doi":"10.1002/advs.78035","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1002/advs.78035","archive_url":"https://space-kitty.com/papers/doi:10.1002/advs.78035","updated":null,"pmid":"42811603","pmcid":"PMC13624414","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13624414/pdf","abstract":"Chronic inflammation drives tissue dysfunction and aging, yet the dynamic interplay between persistent inflammatory signaling and structural deterioration remains difficult to study in human-relevant systems. Here, an advanced long-term human skin platform is presented that preserves native tissue architecture and epidermal, stromal, and immune-associated molecular programs for up to 4 weeks. Time-course RNA sequencing of 199 tissue samples from 20 donors revealed an early culture adaptation phase followed by stabilization of tissue-associated transcriptional programs. Using this system, sustained IL-17/IL-22 stimulation over 3 weeks induced chronic inflammatory transcriptional programs, progressive histopathological changes, and persistent secretion of IL-8, MCP-1, S100A8/A9, and MMP-1, which was broadly suppressed by the Janus kinase inhibitor tofacitinib. In aged donor tissue, prolonged senolytic-associated treatment attenuated inflammatory and remodeling pathways and reduced senescence-associated secretory factors, including IL-6 and MMP-1, with significant treatment-associated effects evident at Week 3 but not Week 1. Finally, ultraviolet B exposure triggered coordinated stress and inflammatory responses that were mitigated using topical sunscreen, demonstrating compatibility with environmental stress modeling and topical intervention. Together, these findings establish a versatile human skin platform for modeling chronic inflammation, aging-associated tissue remodeling, and environmental stress, providing a translational framework for investigating skin tissue dysfunction and evaluating therapeutic interventions.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Long-Term Human Skin Platform for Modeling Chronic Inflammation, Environmental Stress, and Therapeutic Intervention\" by Sharma PK, Schaafsma E, Anderson E et al., https://doi.org/10.1002/advs.78035, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"aging-longevity","name":"Biology of Aging & Longevity","domain_slug":"medicine"}],"cited_in_dossiers":[]}