{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:45:05Z","timestamp":1790671505728,"version":"4.1.0"},"reference-count":82,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":503,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"crossref","award":["31003A_169204"],"award-info":[{"award-number":["31003A_169204"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003357","name":"Gebert R\u00fcf Stiftung","doi-asserted-by":"crossref","award":["052\/13"],"award-info":[{"award-number":["052\/13"]}],"id":[{"id":"10.13039\/501100003357","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Netherton syndrome is a monogenic autosomal recessive disorder primarily characterized by the detachment of the uppermost layer of the epidermis, the stratum corneum. It results from mutations in the SPINK5 gene, which codes for a kallikrein inhibitor. Uncontrolled kallikrein activity leads to premature desquamation, resulting in a severe epidermal barrier defect and consequently life-threatening systemic infections and chronic cutaneous inflammation. Here, we show that genetic activation of the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nfe2l2\/Nrf2) in keratinocytes of Spink5 knockout mice, a model for Netherton syndrome, significantly alleviates their cutaneous phenotype. Nrf2 activation promoted attachment of the stratum corneum and concomitantly epidermal barrier function, and reduced the expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha and thymic stromal lymphopoietin. Mechanistically, we show that Nrf2 activation induces overexpression of secretory leukocyte protease inhibitor (Slpi), a known inhibitor of kallikrein 7 and elastase 2, in mouse and human keratinocytes in vivo and in vitro, respectively. In the Spink5-deficient epidermis, the upregulation of SLPI likely promotes stabilization of corneodesmosomes, thereby preventing premature desquamation. Our results thus suggest pharmacological NRF2 activation as a promising treatment modality for Netherton syndrome patients.<\/jats:p>","DOI":"10.1242\/dmm.042648","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T14:15:21Z","timestamp":1590502521000},"source":"Crossref","is-referenced-by-count":11,"title":["Genetic activation of Nrf2 reduces cutaneous symptoms in a murine model of Netherton syndrome"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9330-4027","authenticated-orcid":false,"given":"Sukalp","family":"Muzumdar","sequence":"first","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Hiebert","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Bapst","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Gravina","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Bloch","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Dietmar","family":"Beer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital of Zurich, Gloriastrasse 3, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7397-8710","authenticated-orcid":false,"given":"Sabine","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042700241906300_DMM042648C1","doi-asserted-by":"publisher","first-page":"6147","DOI":"10.4049\/jimmunol.1301350","article-title":"Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis","volume":"191","author":"Antsiferova","year":"2013","journal-title":"J. Immunol."},{"key":"2021042700241906300_DMM042648C2","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1016\/j.jaci.2018.08.042","article-title":"Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through keratinocyte IL-1alpha release","volume":"143","author":"Archer","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"2021042700241906300_DMM042648C3","doi-asserted-by":"publisher","first-page":"3373","DOI":"10.4049\/jimmunol.178.6.3373","article-title":"Cutting edge: proinflammatory and Th2 cytokines synergize to induce thymic stromal lymphopoietin production by human skin keratinocytes","volume":"178","author":"Bogiatzi","year":"2007","journal-title":"J. Immunol."},{"key":"2021042700241906300_DMM042648C4","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1172\/JCI41440","article-title":"Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing","volume":"120","author":"Bonnart","year":"2010","journal-title":"J. Clin. Invest."},{"key":"2021042700241906300_DMM042648C5","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1084\/jem.20082242","article-title":"Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome","volume":"206","author":"Briot","year":"2009","journal-title":"J. Exp. Med."},{"key":"2021042700241906300_DMM042648C6","doi-asserted-by":"publisher","first-page":"2736","DOI":"10.1038\/jid.2010.233","article-title":"Par2 inactivation inhibits early production of TSLP, but not cutaneous inflammation, in Netherton syndrome adult mouse model","volume":"130","author":"Briot","year":"2010","journal-title":"J. Invest. Dermatol."},{"key":"2021042700241906300_DMM042648C7","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/j.0022-202X.2004.23539.x","article-title":"Agonists of proteinase-activated receptor-2 stimulate upregulation of intercellular cell adhesion molecule-1 in primary human keratinocytes via activation of NF-kappa B","volume":"124","author":"Buddenkotte","year":"2005","journal-title":"J. Invest. Dermatol."},{"key":"2021042700241906300_DMM042648C8","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1111\/j.0022-202X.2004.22512.x","article-title":"Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE\/KLK5\/hK5 and SCCE\/KLK7\/hK7","volume":"122","author":"Caubet","year":"2004","journal-title":"J. Invest. Dermatol."},{"key":"2021042700241906300_DMM042648C9","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/75977","article-title":"Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome","volume":"25","author":"Chavanas","year":"2000","journal-title":"Nat. Genet."},{"key":"2021042700241906300_DMM042648C10","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1086\/302824","article-title":"Localization of the Netherton syndrome gene to chromosome 5q32, by linkage analysis and homozygosity mapping","volume":"66","author":"Chavanas","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"2021042700241906300_DMM042648C11","doi-asserted-by":"publisher","first-page":"7416","DOI":"10.1093\/nar\/gks409","article-title":"Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha","volume":"40","author":"Chorley","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2021042700241906300_DMM042648C12","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1159\/000257290","article-title":"Ichthyosis linearis circumflexa","volume":"98","author":"Com\u00e8l","year":"1949","journal-title":"Dermatology"},{"key":"2021042700241906300_DMM042648C13","doi-asserted-by":"publisher","first-page":"3607","DOI":"10.1091\/mbc.e07-02-0124","article-title":"LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction","volume":"18","author":"Deraison","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"2021042700241906300_DMM042648C14","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/ng1493","article-title":"Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity","volume":"37","author":"Descargues","year":"2005","journal-title":"Nat. Genet."},{"key":"2021042700241906300_DMM042648C15","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1038\/mt.2010.201","article-title":"Ex-vivo gene therapy restores LEKTI activity and corrects the architecture of Netherton syndrome-derived skin grafts","volume":"19","author":"Di","year":"2011","journal-title":"Mol. Ther."},{"key":"2021042700241906300_DMM042648C16","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1089\/humc.2013.195","article-title":"Phase I study protocol for ex vivo lentiviral gene therapy for the inherited skin disease, Netherton syndrome","volume":"24","author":"Di","year":"2013","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"2021042700241906300_DMM042648C17","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1089\/hum.2019.049","article-title":"Generation and clinical application of gene-modified autologous epidermal sheets in Netherton syndrome: lessons learned from a phase 1 trial","volume":"30","author":"Di","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"2021042700241906300_DMM042648C18","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.canlet.2005.09.012","article-title":"Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts","volume":"240","author":"Dinkova-Kostova","year":"2006","journal-title":"Cancer Lett."},{"key":"2021042700241906300_DMM042648C19","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1001\/archderm.135.7.823","article-title":"Altered lamellar body secretion and stratum corneum membrane structure in Netherton syndrome: differentiation from other infantile erythrodermas and pathogenic implications","volume":"135","author":"Fartasch","year":"1999","journal-title":"Arch. Dermatol."},{"key":"2021042700241906300_DMM042648C20","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1038\/jid.2011.124","article-title":"Infliximab infusions for Netherton syndrome: sustained clinical improvement correlates with a reduction of thymic stromal lymphopoietin levels in the skin","volume":"131","author":"Fontao","year":"2011","journal-title":"J. Invest. Dermatol."},{"key":"2021042700241906300_DMM042648C21","doi-asserted-by":"publisher","first-page":"21886","DOI":"10.1074\/jbc.271.36.21886","article-title":"Antileukoprotease inhibits stratum corneum chymotryptic enzyme. Evidence for a regulative function in desquamation","volume":"271","author":"Franzke","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2021042700241906300_DMM042648C22","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1084\/jem.20131797","article-title":"Transgenic kallikrein 5 mice reproduce major cutaneous and systemic hallmarks of Netherton syndrome","volume":"211","author":"Furio","year":"2014","journal-title":"J. Exp. Med."},{"key":"2021042700241906300_DMM042648C23","doi-asserted-by":"publisher","first-page":"e1005389","DOI":"10.1371\/journal.pgen.1005389","article-title":"KLK5 inactivation reverses cutaneous hallmarks of Netherton syndrome","volume":"11","author":"Furio","year":"2015","journal-title":"PLoS Genet."},{"key":"2021042700241906300_DMM042648C24","first-page":"585","article-title":"[Severe hypernatremic dehydration disclosing Netherton syndrome in the neonatal period]","volume":"50","author":"Giroux","year":"1993","journal-title":"Arch. Fr. Pediatr."},{"key":"2021042700241906300_DMM042648C25","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1016\/j.freeradbiomed.2012.10.001","article-title":"Nrf2 in bone marrow-derived cells positively contributes to the advanced stage of atherosclerotic plaque formation","volume":"53","author":"Harada","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"2021042700241906300_DMM042648C26","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1242\/dev.125.8.1541","article-title":"Patterned acquisition of skin barrier function during development","volume":"125","author":"Hardman","year":"1998","journal-title":"Development"},{"key":"2021042700241906300_DMM042648C27","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1111\/j.1525-1470.1996.tb01202.x","article-title":"Severe congenital generalized exfoliative erythroderma in newborns and infants: a possible sign of Netherton syndrome","volume":"13","author":"Hausser","year":"1996","journal-title":"Pediatr. Dermatol."},{"key":"2021042700241906300_DMM042648C28","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/j.1749-6632.2009.05128.x","article-title":"Thymic stromal lymphopoietin","volume":"1183","author":"He","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2021042700241906300_DMM042648C29","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1093\/hmg\/ddi030","article-title":"Lethal, neonatal ichthyosis with increased proteolytic processing of filaggrin in a mouse model of Netherton syndrome","volume":"14","author":"Hewett","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"2021042700241906300_DMM042648C30","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.devcel.2018.06.012","article-title":"Nrf2-mediated fibroblast reprogramming drives cellular senescence by targeting the matrisome","volume":"46","author":"Hiebert","year":"2018","journal-title":"Dev. Cell"},{"key":"2021042700241906300_DMM042648C31","first-page":"428","article-title":"[Netherton syndrome: weakened immunity, generalized verrucosis and carcinogenesis]","volume":"31","author":"Hintner","year":"1980","journal-title":"Hautarzt"},{"key":"2021042700241906300_DMM042648C32","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s00441-013-1558-1","article-title":"Netherton syndrome: skin inflammation and allergy by loss of protease inhibition","volume":"351","author":"Hovnanian","year":"2013","journal-title":"Cell Tissue Res."},{"key":"2021042700241906300_DMM042648C33","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1016\/j.devcel.2012.11.002","article-title":"Amniotic fluid activates the nrf2\/keap1 pathway to repair an epidermal barrier defect in utero","volume":"23","author":"Huebner","year":"2012","journal-title":"Dev. Cell"},{"key":"2021042700241906300_DMM042648C34","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/978-1-61779-191-8_4","article-title":"Epidermal permeability barrier measurement in mammalian skin","volume":"763","author":"Indra","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"2021042700241906300_DMM042648C35","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1111\/j.1365-2133.1986.tb04885.x","article-title":"Neonatal hypernatraemia in two siblings with Netherton's syndrome","volume":"114","author":"Jones","year":"1986","journal-title":"Br. J. Dermatol."},{"key":"2021042700241906300_DMM042648C36","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1111\/j.1365-2133.1994.tb04971.x","article-title":"A clinical and immunological study of Netherton's syndrome","volume":"131","author":"Judge","year":"1994","journal-title":"Br. J. Dermatol."},{"key":"2021042700241906300_DMM042648C37","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1016\/j.devcel.2009.04.013","article-title":"Muscle contraction is necessary to maintain joint progenitor cell fate","volume":"16","author":"Kahn","year":"2009","journal-title":"Dev. Cell"},{"key":"2021042700241906300_DMM042648C38","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1515\/hsz-2016-0194","article-title":"A viable mouse model for Netherton syndrome based on mosaic inactivation of the Spink5 gene","volume":"397","author":"Kasparek","year":"2016","journal-title":"Biol. Chem."},{"key":"2021042700241906300_DMM042648C39","doi-asserted-by":"publisher","first-page":"e1006566","DOI":"10.1371\/journal.pgen.1006566","article-title":"KLK5 and KLK7 ablation fully rescues lethality of Netherton syndrome-like phenotype","volume":"13","author":"Kasparek","year":"2017","journal-title":"PLoS Genet."},{"key":"2021042700241906300_DMM042648C40","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.1172\/JCI84870","article-title":"Oxidative stress and dysfunctional NRF2 underlie pachyonychia congenita phenotypes","volume":"126","author":"Kerns","year":"2016","journal-title":"J. Clin. Invest."},{"key":"2021042700241906300_DMM042648C41","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.phrs.2013.09.009","article-title":"Sulforaphane and phenylethyl isothiocyanate protect human skin against UVR-induced oxidative stress and apoptosis: role of Nrf2-dependent gene expression and antioxidant enzymes","volume":"78","author":"Kleszczy\u0144ski","year":"2013","journal-title":"Pharmacol. Res."},{"key":"2021042700241906300_DMM042648C42","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1083\/jcb.151.2.389","article-title":"Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein","volume":"151","author":"Koch","year":"2000","journal-title":"J. Cell Biol."},{"key":"2021042700241906300_DMM042648C43","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1046\/j.0022-202x.2001.01663.x","article-title":"Elevated stratum corneum hydrolytic activity in Netherton syndrome suggests an inhibitory regulation of desquamation by SPINK5-derived peptides","volume":"118","author":"Komatsu","year":"2002","journal-title":"J. Invest. Dermatol."},{"key":"2021042700241906300_DMM042648C44","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.4049\/jimmunol.0900904","article-title":"Proteases induce production of thymic stromal lymphopoietin by airway epithelial cells through protease-activated receptor-2","volume":"183","author":"Kouzaki","year":"2009","journal-title":"J. Immunol."},{"key":"2021042700241906300_DMM042648C45","doi-asserted-by":"publisher","first-page":"3499S","DOI":"10.1093\/jn\/134.12.3499S","article-title":"Transcription factor Nrf2 is essential for induction of NAD(P)H:quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates","volume":"134","author":"McWalter","year":"2004","journal-title":"J. Nutr."},{"key":"2021042700241906300_DMM042648C46","doi-asserted-by":"publisher","first-page":"3305","DOI":"10.1128\/MCB.00677-14","article-title":"Susceptibility of Nrf2-null mice to steatohepatitis and cirrhosis upon consumption of a high-fat diet is associated with oxidative stress, perturbation of the unfolded protein response, and disturbance in the expression of metabolic enzymes but not with insulin resistance","volume":"34","author":"Meakin","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"2021042700241906300_DMM042648C47","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.rmed.2012.11.006","article-title":"Sulforaphane induces SLPI secretion in the nasal mucosa","volume":"107","author":"Meyer","year":"2013","journal-title":"Respir. Med."},{"key":"2021042700241906300_DMM042648C48","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.ccr.2012.05.016","article-title":"Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming","volume":"22","author":"Mitsuishi","year":"2012","journal-title":"Cancer Cell"},{"key":"2021042700241906300_DMM042648C49","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/j.ajpath.2012.11.039","article-title":"Protease activity enhances production of thymic stromal lymphopoietin and basophil accumulation in flaky tail mice","volume":"182","author":"Moniaga","year":"2013","journal-title":"Am. J. Pathol."},{"key":"2021042700241906300_DMM042648C50","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1001\/archderm.1958.01560100059009","article-title":"A unique case of trichorrhexis nodosa; bamboo hairs","volume":"78","author":"Netherton","year":"1958","journal-title":"AMA Arch. Derm."},{"key":"2021042700241906300_DMM042648C51","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1186\/1471-2407-8-373","article-title":"Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer","volume":"8","author":"Ramani","year":"2008","journal-title":"BMC Cancer"},{"key":"2021042700241906300_DMM042648C52","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1002\/gene.20025","article-title":"A keratin K5Cre transgenic line appropriate for tissue-specific or generalized Cre-mediated recombination","volume":"39","author":"Ramirez","year":"2004","journal-title":"Genesis"},{"key":"2021042700241906300_DMM042648C53","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s12895-015-0029-7","article-title":"Topical application of RTA 408 lotion activates Nrf2 in human skin and is well-tolerated by healthy human volunteers","volume":"15","author":"Reisman","year":"2015","journal-title":"BMC Dermatol."},{"key":"2021042700241906300_DMM042648C54","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.jaci.2009.06.009","article-title":"Com\u00e8l-Netherton syndrome defined as primary immunodeficiency","volume":"124","author":"Renner","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"2021042700241906300_DMM042648C55","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.jdcr.2017.07.019","article-title":"Infliximab therapy for Netherton syndrome: a case report","volume":"3","author":"Roda","year":"2017","journal-title":"JAAD Case Rep."},{"key":"2021042700241906300_DMM042648C56","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.jdermsci.2010.12.004","article-title":"rAAV2-mediated restoration of LEKTI in LEKTI-deficient cells from Netherton patients","volume":"61","author":"Roedl","year":"2011","journal-title":"J. Dermatol. Sci."},{"key":"2021042700241906300_DMM042648C57","doi-asserted-by":"publisher","first-page":"287","DOI":"10.3389\/fphar.2018.00287","article-title":"Topical bixin confers NRF2-dependent protection against photodamage and hair graying in mouse skin","volume":"9","author":"Rojo de la Vega","year":"2018","journal-title":"Front. Pharmacol."},{"key":"2021042700241906300_DMM042648C58","doi-asserted-by":"publisher","first-page":"4817","DOI":"10.1158\/0008-5472.CAN-15-0614","article-title":"Nrf2 activation promotes keratinocyte survival during early skin carcinogenesis via metabolic alterations","volume":"75","author":"Rolfs","year":"2015","journal-title":"Cancer Res."},{"key":"2021042700241906300_DMM042648C59","doi-asserted-by":"publisher","first-page":"S134","DOI":"10.1016\/j.anai.2018.09.443","article-title":"The difficult management of three patients with Netherton syndrome","volume":"121","author":"Saenz","year":"2018","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"2021042700241906300_DMM042648C60","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.freeradbiomed.2015.04.018","article-title":"Nrf2\u2014A regulator of keratinocyte redox signaling","volume":"88","author":"Sch\u00e4fer","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"2021042700241906300_DMM042648C61","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1101\/gad.568810","article-title":"Nrf2 establishes a glutathione-mediated gradient of UVB cytoprotection in the epidermis","volume":"24","author":"Sch\u00e4fer","year":"2010","journal-title":"Genes Dev."},{"key":"2021042700241906300_DMM042648C62","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1002\/emmm.201200219","article-title":"Nrf2 links epidermal barrier function with antioxidant defense","volume":"4","author":"Sch\u00e4fer","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"2021042700241906300_DMM042648C63","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1002\/emmm.201303281","article-title":"Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice","volume":"6","author":"Sch\u00e4fer","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"2021042700241906300_DMM042648C64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/jid.2014.495","article-title":"Assessing the in vivo epidermal barrier in mice: dye penetration assays","volume":"135","author":"Schmitz","year":"2015","journal-title":"J. Invest. Dermatol."},{"key":"2021042700241906300_DMM042648C65","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/S0091-6749(95)70159-1","article-title":"Netherton's syndrome: a syndrome of elevated IgE and characteristic skin and hair findings","volume":"95","author":"Smith","year":"1995","journal-title":"J. Allergy Clin. Immunol."},{"key":"2021042700241906300_DMM042648C66","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.4049\/jimmunol.1101620","article-title":"Caspase-4 is required for activation of inflammasomes","volume":"188","author":"Sollberger","year":"2012","journal-title":"J. Immunol."},{"key":"2021042700241906300_DMM042648C67","first-page":"237","article-title":"Severe hypernatremic dehydration in an infant with Netherton syndrome","volume":"12","author":"Stoll","year":"2001","journal-title":"Genet. Couns."},{"key":"2021042700241906300_DMM042648C68","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1046\/j.1525-1470.1999.99005.x","article-title":"Selective antibody deficiency to bacterial polysaccharide antigens in patients with Netherton syndrome","volume":"16","author":"Stryk","year":"1999","journal-title":"Pediatr. Dermatol."},{"key":"2021042700241906300_DMM042648C69","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1111\/j.1365-4632.2005.02637.x","article-title":"Netherton syndrome: a case report and review of the literature","volume":"45","author":"Sun","year":"2006","journal-title":"Int. J. Dermatol."},{"key":"2021042700241906300_DMM042648C70","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/S0304-3940(96)13141-4","article-title":"Movements of mouse fetuses in early stages of neural development studied in vitro","volume":"218","author":"Suzue","year":"1996","journal-title":"Neurosci. Lett."},{"key":"2021042700241906300_DMM042648C71","doi-asserted-by":"publisher","first-page":"re3","DOI":"10.1126\/scisignal.3112re3","article-title":"Stress-activated cap\u2018n'collar transcription factors in aging and human disease","volume":"3","author":"Sykiotis","year":"2010","journal-title":"Sci. Signal."},{"key":"2021042700241906300_DMM042648C72","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1089\/ars.2017.7342","article-title":"Transcriptional regulation by Nrf2","volume":"29","author":"Tonelli","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"2021042700241906300_DMM042648C73","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1038\/jid.2013.517","article-title":"Intercellular skin barrier lipid composition and organization in Netherton syndrome patients","volume":"134","author":"van Smeden","year":"2014","journal-title":"J. Invest. Dermatol."},{"key":"2021042700241906300_DMM042648C74","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.febslet.2011.12.022","article-title":"Double-stranded RNA induces S100 gene expression by a cycloheximide-sensitive factor","volume":"586","author":"Voss","year":"2012","journal-title":"FEBS Lett."},{"key":"2021042700241906300_DMM042648C75","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1001\/archderm.1964.01590250052010","article-title":"Netherton's disease; trichorrhexis invaginata (bamboo hair), congenital ichthyosiform erythroderma and the atopic diathesis. a histopathologic study","volume":"89","author":"Wilkinson","year":"1964","journal-title":"Arch. Dermatol."},{"key":"2021042700241906300_DMM042648C76","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.iac.2015.05.004","article-title":"Eosinophilia associated with disorders of immune deficiency or immune dysregulation","volume":"35","author":"Williams","year":"2015","journal-title":"Immunol. Allergy Clin. North Am."},{"key":"2021042700241906300_DMM042648C77","doi-asserted-by":"publisher","first-page":"eaat8329","DOI":"10.1126\/scitranslmed.aat8329","article-title":"Quorum sensing between bacterial species on the skin protects against epidermal injury in atopic dermatitis","volume":"11","author":"Williams","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"2021042700241906300_DMM042648C78","doi-asserted-by":"publisher","first-page":"8293","DOI":"10.1158\/0008-5472.CAN-06-0300","article-title":"Inhibition of 7,12-dimethylbenz(a)anthracene-induced skin tumorigenesis in C57BL\/6 mice by sulforaphane is mediated by nuclear factor E2-related factor 2","volume":"66","author":"Xu","year":"2006","journal-title":"Cancer Res."},{"key":"2021042700241906300_DMM042648C79","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1152\/physrev.00023.2017","article-title":"The KEAP1-NRF2 system: a Thiol-based sensor-effector apparatus for maintaining redox homeostasis","volume":"98","author":"Yamamoto","year":"2018","journal-title":"Physiol. Rev."},{"key":"2021042700241906300_DMM042648C80","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.1101\/gad.1232104","article-title":"Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5\u2212\/\u2212 mice","volume":"18","author":"Yang","year":"2004","journal-title":"Genes Dev."},{"key":"2021042700241906300_DMM042648C81","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1083\/jcb.200910126","article-title":"Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis","volume":"188","author":"Yang","year":"2010","journal-title":"J. Cell Biol."},{"key":"2021042700241906300_DMM042648C82","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.ajpath.2015.09.005","article-title":"S100A8 and S100A9 are induced by decreased hydration in the epidermis and promote fibroblast activation and fibrosis in the dermis","volume":"186","author":"Zhong","year":"2016","journal-title":"Am. J. Pathol."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dmm.042648","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.042648\/1973555\/dmm042648.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.042648\/2065900\/dmm_042648v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.042648\/2065900\/dmm_042648v1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T22:44:14Z","timestamp":1621377854000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/doi\/10.1242\/dmm.042648\/267187\/Genetic-activation-of-Nrf2-reduces-cutaneous"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,1]]},"references-count":82,"URL":"https:\/\/doi.org\/10.1242\/dmm.042648","relation":{},"ISSN":["1754-8411","1754-8403"],"issn-type":[{"value":"1754-8411","type":"electronic"},{"value":"1754-8403","type":"print"}],"subject":[],"published":{"date-parts":[[2020,1,1]]},"article-number":"dmm.042648"}}