{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:55:04Z","timestamp":1790243704432,"version":"4.1.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"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. Immunol."],"DOI":"10.3389\/fimmu.2020.01740","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T05:20:48Z","timestamp":1597209648000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":73,"title":["Protease-Activated Receptor-2 Regulates Neuro-Epidermal Communication in Atopic Dermatitis"],"prefix":"10.3389","volume":"11","author":[{"given":"Timo","family":"Buhl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Ikoma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordula","family":"Kempkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferda","family":"Cevikbas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Sulk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Buddenkotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasuku","family":"Akiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Crumrine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Camerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Earl","family":"Carstens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Sch\u00f6n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Elias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun R.","family":"Coughlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Steinhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1124\/pr.54.2.203","article-title":"International Union of Pharmacology. XXVIII. Proteinase-activated receptors","volume":"54","author":"Hollenberg","year":"2002","journal-title":"Pharmacol Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1210\/er.2003-0025","article-title":"Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response","volume":"26","author":"Steinhoff","year":"2005","journal-title":"Endocr Rev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/1478-811X-11-86","article-title":"Proteinase-activated receptors (PARs) - focus on receptor-receptor-interactions and their physiological and pathophysiological impact","volume":"11","author":"Gieseler","year":"2013","journal-title":"Cell Commun Signal."},{"key":"B4","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/72247","article-title":"Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism","volume":"6","author":"Steinhoff","year":"2000","journal-title":"Nat Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1038\/89945","article-title":"Proteinase-activated receptor-2 and hyperalgesia: a novel pain pathway","volume":"7","author":"Vergnolle","year":"2001","journal-title":"Nat Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/ncomms1162","article-title":"PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1\/Prss8 expression in mouse skin","volume":"2","author":"Frateschi","year":"2011","journal-title":"Nat Commun."},{"key":"B7","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1172\/JCI17564","article-title":"PARticipation in inflammation","volume":"111","author":"Coughlin","year":"2003","journal-title":"J Clin Invest."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2598","DOI":"10.4049\/jimmunol.175.4.2598","article-title":"Protease-activated receptor-2 activation induces acute lung inflammation by neuropeptide-dependent mechanisms","volume":"175","author":"Su","year":"2005","journal-title":"J Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1124\/jpet.111.187062","article-title":"Antagonism of protease-activated receptor 2 protects against experimental colitis","volume":"340","author":"Lohman","year":"2012","journal-title":"J Pharmacol Exp Ther."},{"key":"B10","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1172\/JCI29255","article-title":"Role for protease activity in visceral pain in irritable bowel syndrome","volume":"117","author":"Cenac","year":"2007","journal-title":"J Clin Invest."},{"key":"B11","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1084\/jem.20052148","article-title":"Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis","volume":"203","author":"Noorbakhsh","year":"2006","journal-title":"J Exp Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"7320","DOI":"10.4049\/jimmunol.174.11.7320","article-title":"Proteinase-activated receptor-2 induction by neuroinflammation prevents neuronal death during HIV infection","volume":"174","author":"Noorbakhsh","year":"2005","journal-title":"J Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1128\/IAI.01019-09","article-title":"Protease-activated receptor 2 has pivotal roles in cellular mechanisms involved in experimental periodontitis","volume":"78","author":"Wong","year":"2010","journal-title":"Infect Immun."},{"key":"B14","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.jaci.2014.05.048","article-title":"Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier in patients with atopic dermatitis","volume":"134","author":"Elias","year":"2014","journal-title":"J Allergy Clin Immunol."},{"key":"B15","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":"B16","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":"B17","doi-asserted-by":"publisher","first-page":"808","DOI":"10.3349\/ymj.2010.51.6.808","article-title":"Protease and protease-activated receptor-2 signaling in the pathogenesis of atopic dermatitis","volume":"51","author":"Lee","year":"2010","journal-title":"Yonsei Med J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1189\/jlb.0503221","article-title":"Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices","volume":"76","author":"Shpacovitch","year":"2004","journal-title":"J Leukoc Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1111\/j.1600-0625.2010.01184.x","article-title":"Role of protease-activated receptors in human skin fibrosis and scleroderma","volume":"20","author":"Cevikbas","year":"2011","journal-title":"Exp Dermatol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1006\/excr.1999.4692","article-title":"The protease-activated receptor 2 regulates pigmentation via keratinocyte-melanocyte interactions","volume":"254","author":"Seiberg","year":"2000","journal-title":"Exp Cell Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3814","DOI":"10.1111\/bph.12738","article-title":"Serine proteases and protease-activated receptor 2 mediate the proinflammatory and algesic actions of diverse stimulants","volume":"171","author":"Cattaruzza","year":"2014","journal-title":"Br J Pharmacol."},{"key":"B22","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":"B23","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1056\/NEJMra074081","article-title":"Atopic dermatitis","volume":"358","author":"Bieber","year":"2008","journal-title":"N Engl J Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1016\/j.jaci.2012.07.012","article-title":"Progressive activation of T(H)2\/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis","volume":"130","author":"Gittler","year":"2012","journal-title":"J Allergy Clin Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.jaci.2012.06.048","article-title":"Atopic dermatitis results in intrinsic barrier and immune abnormalities: implications for contact dermatitis","volume":"131","author":"Gittler","year":"2013","journal-title":"J Allergy Clin Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"858","DOI":"10.3390\/jcm4050858","article-title":"Immune pathways in atopic dermatitis, and definition of biomarkers through broad and targeted therapeutics","volume":"4","author":"Mansouri","year":"2015","journal-title":"J Clin Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1038\/jid.2008.88","article-title":"\u201cOutside-to-inside\u201d (and now back to \u201coutside\u201d) pathogenic mechanisms in atopic dermatitis","volume":"128","author":"Elias","year":"2008","journal-title":"J Invest Dermatol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.jaci.2006.03.047","article-title":"Cytokines and chemokines orchestrate atopic skin inflammation","volume":"118","author":"Homey","year":"2006","journal-title":"J Allergy Clin Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"86","DOI":"10.2353\/ajpath.2008.070161","article-title":"Acute modulations in permeability barrier function regulate epidermal cornification: role of caspase-14 and the protease-activated receptor type 2","volume":"172","author":"Demerjian","year":"2008","journal-title":"Am J Pathol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1038\/jid.2008.13","article-title":"Mite and cockroach allergens activate protease-activated receptor 2 and delay epidermal permeability barrier recovery","volume":"128","author":"Jeong","year":"2008","journal-title":"J Invest Dermatol."},{"key":"B31","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-\u03baB","volume":"124","author":"Buddenkotte","year":"2005","journal-title":"J Invest Dermatol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1111\/j.1398-9995.2009.02023.x","article-title":"Mite serine protease activates protease-activated receptor-2 and induces cytokine release in human keratinocytes","volume":"64","author":"Kato","year":"2009","journal-title":"Allergy."},{"key":"B33","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":"B34","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1093\/intimm\/9.3.461","article-title":"Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC\/Nga mice","volume":"9","author":"Matsuda","year":"1997","journal-title":"Int Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"6176","DOI":"10.1523\/JNEUROSCI.23-15-06176.2003","article-title":"Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin","volume":"23","author":"Steinhoff","year":"2003","journal-title":"J Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1111\/cea.12185","article-title":"Proteinase-activated receptor-2 activation participates in allergic sensitization to house dust mite allergens in a murine model","volume":"43","author":"Davidson","year":"2013","journal-title":"Clin Exp Allergy."},{"key":"B37","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.cell.2013.08.057","article-title":"The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch","volume":"155","year":"2013","journal-title":"Cell."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2683","DOI":"10.1172\/JCI67323","article-title":"Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus","volume":"124","author":"Kido-Nakahara","year":"2014","journal-title":"J Clin Invest."},{"key":"B39","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":"B40","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/B978-0-12-404717-4.00004-4","article-title":"The biology of thymic stromal lymphopoietin (TSLP)","volume":"66","author":"Ziegler","year":"2013","journal-title":"Adv Pharmacol."},{"key":"B41","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":"B42","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.jaci.2013.08.046","article-title":"Tmem79\/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects","volume":"132","author":"Saunders","year":"2013","journal-title":"J Allergy Clin Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1016\/j.jaci.2012.01.068","article-title":"Altered stratum corneum barrier and enhanced percutaneous immune responses in filaggrin-null mice","volume":"129","author":"Kawasaki","year":"2012","journal-title":"J Allergy Clin Immunol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1177\/1753425913503387","article-title":"Protease-activated receptor-2 deficient mice have reduced house dust mite-evoked allergic lung inflammation","volume":"20","author":"de Boer","year":"2014","journal-title":"Innate Immun."},{"key":"B45","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1113\/expphysiol.2011.060764","article-title":"House dust mite potentiates capsaicin-evoked Ca2+ transients in mouse pulmonary sensory neurons via activation of protease-activated receptor-2","volume":"97","author":"Gu","year":"2012","journal-title":"Exp Physiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/nrm1619","article-title":"The cornified envelope: a model of cell death in the skin","volume":"6","author":"Candi","year":"2005","journal-title":"Nat Rev Mol Cell Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1046\/j.1523-1747.2002.19622.x","article-title":"Origin of the epidermal calcium gradient: regulation by barrier status and role of active vs passive mechanisms","volume":"119","author":"Elias","year":"2002","journal-title":"J Invest Dermatol."},{"key":"B48","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":"B49","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/j.jaci.2013.10.048","article-title":"A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: Involvement of TRPV1 and TRPA1","volume":"133","author":"Cevikbas","year":"2014","journal-title":"J Allergy Clin Immunol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.pain.2010.07.024","article-title":"Enhanced scratching evoked by PAR-2 agonist and 5-HT but not histamine in a mouse model of chronic dry skin itch","volume":"151","author":"Akiyama","year":"2010","journal-title":"Pain."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1097\/j.pain.0000000000000172","article-title":"A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch","volume":"156","author":"Akiyama","year":"2015","journal-title":"Pain."},{"key":"B52","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.neulet.2014.03.062","article-title":"Enhanced scratching elicited by a pruritogen and an algogen in a mouse model of contact hypersensitivity","volume":"579","author":"Fu","year":"2014","journal-title":"Neurosci Lett."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/j.jaci.2012.12.1566","article-title":"Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin","volume":"131","author":"Pellerin","year":"2013","journal-title":"J Allergy Clin Immunol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"79","DOI":"10.5415\/apallergy.2013.3.2.79","article-title":"Overview of atopic dermatitis","volume":"3","author":"Kim","year":"2013","journal-title":"Asia Pac Allergy."},{"key":"B55","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.it.2015.10.006","article-title":"The multi-modal immune pathogenesis of atopic eczema","volume":"36","author":"Eyerich","year":"2015","journal-title":"Trends Immunol."},{"key":"B56","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."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.01740\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T05:20:51Z","timestamp":1597209651000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.01740\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,12]]},"references-count":56,"alternative-id":["10.3389\/fimmu.2020.01740"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.01740","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,12]]},"article-number":"1740"}}