{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T06:24:23Z","timestamp":1787293463299,"version":"build-2736575974"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"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. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Epidermolysis bullosa simplex (EBS) is a genetic skin disorder driven by dominant pathogenic variants in\n                    <jats:italic>KRT5<\/jats:italic>\n                    or\n                    <jats:italic>KRT14<\/jats:italic>\n                    genes, leading to cytoskeletal fragility in basal keratinocytes and intraepidermal blistering. No curative therapies are currently available, and the link between keratin mutations and disease mechanisms remains incompletely understood. To further investigate the inflammatory component of EBS, we used a model of hiPSC-derived keratinocytes carrying dominant\n                    <jats:italic>KRT5<\/jats:italic>\n                    variants, alongside a genetically corrected isogenic counterpart. This approach established a direct link between the\n                    <jats:italic>KRT5<\/jats:italic>\n                    variants and keratin aggregation, impaired proliferation, and an inflammatory phenotype. The inflammatory signature was confirmed by increased expression of IL1A and IL1B, consistent with previous observations in EBS, while CXCL10 and CXCL11 emerged as newly identified dysregulated chemokines. Their consistent increase across independent cell lines, elevated secretion, and normalization in the CRISPR-corrected isogenic cells indicate that\n                    <jats:italic>KRT5<\/jats:italic>\n                    variants trigger a keratinocyte-intrinsic CXCL10\/CXCL11 inflammatory response. Pharmacological inhibition of the IFN-\u03b3-JAK1\/2-STAT1 pathway suppressed their secretion, supporting JAK inhibition as a potential therapeutic strategy to modulate EBS-associated inflammatory dysregulation. In conclusion, this study shows that beyond structural defects,\n                    <jats:italic>KRT5<\/jats:italic>\n                    variants establish a keratinocyte-intrinsic inflammatory phenotype in which the CXCL10 and CXCL11 axis emerges as a key disease-associated signature and a promising therapeutic target.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1918694","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:37:43Z","timestamp":1787290663000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["An isogenic hiPSC-derived keratinocyte model reveals CXCL10\/CXCL11 inflammatory dysregulation in epidermolysis bullosa simplex"],"prefix":"10.3389","volume":"14","author":[{"given":"Manoubia","family":"Saidani","sequence":"first","affiliation":[{"name":"CECS\/AFM, I- STEM","place":["Corbeil-Essonnes, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Martineau","sequence":"additional","affiliation":[{"name":"INSERM\/UEPS UMR 861, Paris Saclay University, I-STEM","place":["Corbeil-Essonnes, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Human Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre (NRC)","place":["Cairo, Egypt"]},{"name":"Stem Cell Research Unit, Medical Research Centre of Excellence, NRC","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Domingues","sequence":"additional","affiliation":[{"name":"CECS\/AFM, I- STEM","place":["Corbeil-Essonnes, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Doyen","sequence":"additional","affiliation":[{"name":"INSERM\/UEPS UMR 861, Paris Saclay University, I-STEM","place":["Corbeil-Essonnes, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"El Kassar","sequence":"additional","affiliation":[{"name":"CECS\/AFM, I- STEM","place":["Corbeil-Essonnes, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smail","family":"Hadj-Rabia","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Reference Centre for Genodermatoses and Rare Skin Disease (MAGEC), Fili\u00e8re FIMARAD, Hopital Universitaire Necker-Enfants Malades, APHP-Centre","place":["Paris, France"]},{"name":"Paris Cite University","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bodemer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Reference Centre for Genodermatoses and Rare Skin Disease (MAGEC), Fili\u00e8re FIMARAD, Hopital Universitaire Necker-Enfants Malades, APHP-Centre","place":["Paris, France"]},{"name":"Paris Cite University","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Allouche","sequence":"additional","affiliation":[{"name":"INSERM\/UEPS UMR 861, Paris Saclay University, I-STEM","place":["Corbeil-Essonnes, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Baldeschi","sequence":"additional","affiliation":[{"name":"INSERM\/UEPS UMR 861, Paris Saclay University, I-STEM","place":["Corbeil-Essonnes, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Holic","sequence":"additional","affiliation":[{"name":"INSERM\/UEPS UMR 861, Paris Saclay University, I-STEM","place":["Corbeil-Essonnes, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2298","DOI":"10.1016\/j.jid.2017.07.002","article-title":"Pro-Inflammatory chemokines and cytokines dominate the blister fluid molecular signature in patients with epidermolysis bullosa and affect leukocyte and stem cell migration","volume":"137","author":"Alexeev","year":"2017","journal-title":"J. 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