ENAGenomicsGenomics and Immunoregulation, LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)https://www.ebi.ac.uk/ena/browser/view/PRJNA146469Mus musculusKeratin 1 (KRT1) and its heterodimer partner keratin 10 (KRT10) constitute the intermediate filament cytoskeleton of suprabasal skin keratinocytes. They participate in formation of the epidermal barrier, which protects against dehydration and inflammation. Mutations in KRT1 cause keratinopathic ichthyosis with erythema, recurrent inflammation, and barrier defects. Here, we show that genetic deletion of Krt1 in mice causes a defective inside-out epidermal barrier, pre- and postnatal increases in Mrp8/Mrp14, interleukin (IL) 18, IL-33, and thymic stromal lymphopoietin (TSLP) in skin extracts, and systemic release of IL-18 into newborn serum. Perinatal lethality was partially rescued by treatment with glucocorticoids to promote barrier repair or with IL- 18-blocking antibodies in utero. In human keratinocytes, IL-18 release was cellautonomous and caspase-1-dependent, indicating KRT1-dependent inflammasome activation. Our data reveal a novl function of KRT1 in controlling inflammasome activity and stimulating barrier formation, thereby integrating the keratin cytoskeleton into the epidermal immune response. In view of their widespread expression, keratins merit investigation of their functions in inflammatory conditions, including asthma and inflammatory bowel disorders. Overall design: Total RNA was obtained from epidermis or full-thickness skin of Krt1+/+ and Krt1-/- mice (C57BL/6 background) at P0 (newborn).ENAdermis plus epidermis plus hypodermis, the integument, Krt-2.1, region of skin, Oct-11a, wide/broad, EHK, EHK1, pelt, determination, Otf-11, Skn-li, Gene, skin zone, integumental organ, broad, hypodermis, Kb1, Krt2-1, epidermis, skin plus hypodermis, Oct11, skin region, chemical analysis, BC033609, Skin-1a, tegument, Skin, integumentum commune, skin benign neoplasm, EPPK, K1, Gene Expressions, CK1, skin, Genomes, vertebrate integument, dermoid system, entire skin, whole genome, outer epithelial layer, Skn-1a., Expressions, SKIN, Krt86, mKIAA0493, NEPPK, Epoc-1, skin organ, portion of skin, wide, vertebrate epidermis, integument, Fam91a1, Otf11, assay, Expression, epidermis (sensu Metazoa), outer epidermal layer, entire integument, KRT1A, hypoderm, AV220772, dermal system, skin and subcutaneous tissueMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisfalseMus musculusGenome-wide analysis of gene expression in Krt1+/+ versus Krt1-/- epidermis and full-thickness skin.2025-09-242014-02-11PRJNA146469GSE3295110090