{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T23:13:29Z","timestamp":1794611609992,"version":"4.9.1"},"reference-count":50,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T00:00:00Z","timestamp":1669507200000},"content-version":"am","delay-in-days":391,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jdsjournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Dermatological Science"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1016\/j.jdermsci.2021.10.006","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:34:21Z","timestamp":1635381261000},"page":"76-82","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"title":["Pathological functions of granzyme B in inflammatory skin diseases"],"prefix":"10.1016","volume":"104","author":[{"given":"Sho","family":"Hiroyasu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoi","family":"Hiroyasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Granville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Tsuruta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"19","key":"10.1016\/j.jdermsci.2021.10.006_bib1","first-page":"19","article-title":"The immunological anatomy of the skin","volume":"191","author":"Kabashima","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/nri3646","article-title":"Mechanisms regulating skin immunity and inflammation","volume":"14","author":"Pasparakis","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib3","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.matbio.2017.12.005","article-title":"Granzyme B in skin inflammation and disease","volume":"75\u201376","author":"Turner","year":"2019","journal-title":"Matrix Biol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-20604-3","article-title":"Granzyme B inhibition reduces disease severity in autoimmune blistering diseases","volume":"12","author":"Hiroyasu","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib5","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.jid.2020.06.013","article-title":"The possible linkage of granzyme B-producing skin T cells with the disease prognosis of alopecia areata","volume":"141","author":"Koguchi-yoshioka","year":"2020","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib6","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jid.2020.05.095","article-title":"Granzyme B contributes to barrier dysfunction in oxazolone-induced skin inflammation through E-cadherin and FLG cleavage","volume":"141","author":"Turner","year":"2020","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib7","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1016\/j.jid.2018.03.1507","article-title":"Blockade of granzyme B remarkably improves mucocutaneous diseases with keratinocyte death in interface dermatitis","volume":"138","author":"Saito","year":"2018","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib8","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1146\/annurev.immunol.26.021607.090404","article-title":"Death by a thousand cuts: granzyme pathways of programmed cell death","volume":"26","author":"Chowdhury","year":"2008","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib9","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1084\/jem.186.10.1781","article-title":"In vitro- and ex vivo-derived cytolytic leukocytes from granzyme A X B double knockout mice are defective in granule-mediated apoptosis but not lysis of target cells","volume":"186","author":"Simon","year":"1997","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib10","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1080\/14728222.2019.1661380","article-title":"Granzyme B as a therapeutic target for wound healing","volume":"23","author":"Turner","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.jdermsci.2021.10.006_bib11","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1002\/eji.1830250432","article-title":"Serial killing by cytotoxic T lymphocytes: T cell receptor triggers degranulation, re-filling of the lytic granules and secretion of lytic proteins via a non-granule pathway","volume":"25","author":"Isaaz","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib12","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/cdd.2009.169","article-title":"Control of granzymes by serpins","volume":"17","author":"Kaiserman","year":"2010","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib13","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/0092-8674(94)90376-X","article-title":"Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells","volume":"76","author":"Heusel","year":"1994","journal-title":"Cell"},{"key":"10.1016\/j.jdermsci.2021.10.006_bib14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41514-021-00059-6","article-title":"Granzyme B mediates impaired healing of pressure injuries in aged skin","volume":"7","author":"Turner","year":"2021","journal-title":"NPJ Aging Mech. Dis."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib15","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1159\/000074128","article-title":"Association of granzyme-B-positive lymphocytes in regressing plane warts","volume":"207","author":"Yamamoto","year":"2003","journal-title":"Dermatology"},{"key":"10.1016\/j.jdermsci.2021.10.006_bib16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-28070-0","article-title":"Granzyme B is elevated in autoimmune blistering diseases and cleaves key anchoring proteins of the dermal-epidermal junction","volume":"8","author":"Russo","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib17","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1046\/j.1523-1747.2000.00828.x","article-title":"Role of cytotoxic T cells in chronic alopecia areata","volume":"114","author":"Bodemer","year":"2000","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib18","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1046\/j.1365-2133.2001.04222.x","article-title":"Perforin and granzyme B may contribute to skin inflammation in atopic dermatitis and psoriasis","volume":"144","author":"Yawalkar","year":"2001","journal-title":"Br. J. Dermatol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib19","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1046\/j.1523-1747.2002.01622.x","article-title":"Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis","volume":"118","author":"Nassif","year":"2002","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib20","doi-asserted-by":"crossref","first-page":"6301","DOI":"10.4049\/jimmunol.1100891","article-title":"Granzyme B regulates antiviral CD8\u2009+\u2009T cell responses","volume":"187","author":"Salti","year":"2011","journal-title":"J. Immunol."},{"issue":"19","key":"10.1016\/j.jdermsci.2021.10.006_bib21","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/s41577-019-0162-3","article-title":"T cells and the skin: from protective immunity to inflammatory skin disorders","volume":"198","author":"Ho","year":"2019","journal-title":"Nat. Rev. Immunol"},{"key":"10.1016\/j.jdermsci.2021.10.006_bib22","first-page":"1","article-title":"Natural killer cells in antiviral immunity","volume":"2021","author":"Bj\u00f6rkstr\u00f6m","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib23","doi-asserted-by":"crossref","DOI":"10.1172\/JCI141594","article-title":"Extracellular traps released by antimicrobial TH17 cells contribute to host defense","volume":"131","author":"Agak","year":"2021","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib24","doi-asserted-by":"crossref","first-page":"750","DOI":"10.12688\/f1000research.11120.1","article-title":"Leishmaniasis: a review","volume":"6","author":"Torres-Guerrero","year":"2017","journal-title":"F1000Research"},{"key":"10.1016\/j.jdermsci.2021.10.006_bib25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003504","article-title":"Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis","volume":"9","author":"Novais","year":"2013","journal-title":"PLOS Pathog."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib26","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/jid.2014.396","article-title":"Proteome profiling of human cutaneous leishmaniasis lesion","volume":"135","author":"Da Silva Santos","year":"2015","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib27","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1093\/infdis\/jiz538","article-title":"Granzyme B produced by natural killer cells enhances inflammatory response and contributes to the immunopathology of cutaneous leishmaniasis","volume":"221","author":"Campos","year":"2020","journal-title":"J. Infect. Dis"},{"key":"10.1016\/j.jdermsci.2021.10.006_bib28","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jid.2020.07.011","article-title":"Granzyme B inhibition by tofacitinib blocks the pathology induced by CD8 T cells in cutaneous leishmaniasis","volume":"141","author":"Novais","year":"2021","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib29","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.3389\/fimmu.2019.01454","article-title":"Proteases in pemphigoid diseases","volume":"10","author":"Hiroyasu","year":"2019","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib30","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1136\/jcp.2006.037010","article-title":"Immunohistological analysis of immune cells in blistering skin lesions","volume":"60","author":"Hussein","year":"2007","journal-title":"J. Clin. Pathol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib31","first-page":"1","article-title":"Alopecia areata","volume":"3","author":"Pratt","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib32","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nm.3645","article-title":"Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition","volume":"20","author":"Xing","year":"2014","journal-title":"Nat. Med."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib33","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1111\/bjd.19040","article-title":"Frontal fibrosing alopecia shows robust T helper 1 and Janus kinase 3 skewing","volume":"183","author":"Del Duca","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib34","doi-asserted-by":"crossref","DOI":"10.1038\/s12276-018-0095-0","article-title":"Topical small molecule granzyme B inhibitor improves remodeling in a murine model of impaired burn wound healing","volume":"50","author":"Shen","year":"2018","journal-title":"Exp. Mol. Med."},{"issue":"2","key":"10.1016\/j.jdermsci.2021.10.006_bib35","article-title":"Serpina3n attenuates granzyme B-mediated decorin cleavage and rupture in a murine model of aortic aneurysm","volume":"29","author":"Ang","year":"2011","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib36","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.alit.2020.02.006","article-title":"Japanese guidelines for atopic dermatitis 2020","volume":"69","author":"Katoh","year":"2020","journal-title":"Allergol. Int."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib37","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s41232-017-0044-7","article-title":"The etiopathogenesis of atopic dermatitis: Barrier disruption, immunological derangement, and pruritus","volume":"37","author":"Rerknimitr","year":"2017","journal-title":"Inflamm. Regen."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib38","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jdermsci.2016.09.009","article-title":"Relationships among plasma granzyme B level, pruritus and dermatitis in patients with atopic dermatitis","volume":"84","author":"Kamata","year":"2016","journal-title":"J. Dermatol. Sci."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib39","doi-asserted-by":"crossref","DOI":"10.1172\/JCI130324","article-title":"Maternal diesel particle exposure promotes offspring asthma through NK cell-derived granzyme B","author":"Qian","year":"2020","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib40","doi-asserted-by":"crossref","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":"10.1016\/j.jdermsci.2021.10.006_bib41","first-page":"1","article-title":"PAR2 mediates itch via TRPV3 signaling in keratinocytes","volume":"2","author":"Zhao","year":"2020","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib42","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jdermsci.2015.03.001","article-title":"Clinical perspectives and murine models of lichenoid tissue reaction\/interface dermatitis","volume":"78","author":"Okiyama","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib43","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.jaci.2004.07.047","article-title":"Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells","volume":"114","author":"Nassif","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib44","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1067\/mai.2002.120563","article-title":"Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity","volume":"109","author":"Posadas","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib45","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jaad.2013.11.015","article-title":"Generalized bullous fixed drug eruption is distinct from Stevens-Johnson syndrome\/toxic epidermal necrolysis by immunohistopathological features","volume":"70","author":"Cho","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib46","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2014.423","article-title":"Serpina3n accelerates tissue repair in a diabetic mouse model of delayed wound healing","volume":"5","author":"Hsu","year":"2014","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.jdermsci.2021.10.006_bib47","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.exger.2011.02.004","article-title":"Granzyme B contributes to extracellular matrix remodeling and skin aging in apolipoprotein E knockout mice","volume":"46","author":"Hiebert","year":"2011","journal-title":"Exp. Gerontol."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib48","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/acel.12298","article-title":"Granzyme B mediates both direct and indirect cleavage of extracellular matrix in skin after chronic low-dose ultraviolet light irradiation","volume":"14","author":"Parkinson","year":"2015","journal-title":"Aging Cell"},{"key":"10.1016\/j.jdermsci.2021.10.006_bib49","doi-asserted-by":"crossref","first-page":"8157","DOI":"10.1074\/jbc.M607436200","article-title":"UVA induces granzyme B in human keratinocytes through MIF: implication in extracellular matrix remodeling","volume":"282","author":"Hernandez-Pigeon","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jdermsci.2021.10.006_bib50","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.jaad.2021.05.050","article-title":"Efficacy and safety of the oral Janus kinase inhibitor baricitinib in the treatment of adults with alopecia areata: phase 2 results from a randomized controlled study","volume":"85","author":"King","year":"2021","journal-title":"J. Am. Acad. Dermatol."}],"container-title":["Journal of Dermatological Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0923181121002541?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0923181121002541?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T04:52:04Z","timestamp":1760331124000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0923181121002541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["S0923181121002541"],"URL":"https:\/\/doi.org\/10.1016\/j.jdermsci.2021.10.006","relation":{},"ISSN":["0923-1811"],"issn-type":[{"value":"0923-1811","type":"print"}],"subject":[],"published":{"date-parts":[[2021,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pathological functions of granzyme B in inflammatory skin diseases","name":"articletitle","label":"Article Title"},{"value":"Journal of Dermatological Science","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jdermsci.2021.10.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}