{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:04:37Z","timestamp":1789376677212,"version":"build-2803163510"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Allergic contact dermatitis is a chronic T cell\u2013driven inflammatory skin disease that is caused by repeated exposure to contact allergens. Based on murine studies of acute contact hypersensitivity, mast cells (MCs) are believed to play a role in its pathogenesis. The role of MCs in chronic allergic contact dermatitis has not been investigated, in part because of the lack of murine models for chronic contact hypersensitivity. We developed and used a chronic contact hypersensitivity model in wild-type and MC-deficient mice and assessed skin inflammatory responses to identify and characterize the role of MCs in chronic allergic contact dermatitis. Ear swelling chronic contact hypersensitivity responses increased markedly, up to 4-fold, in MC-deficient KitW-sh\/W-sh (Sash) and MCPT5-Cre+iDTR+ mice compared with wild-type mice. Local engraftment with MCs protected Sash mice from exacerbated ear swelling after repeated oxazolone challenge. Chronic contact hypersensitivity skin of Sash mice exhibited elevated levels of IFN-\u03b3, IL-17\u03b1, and IL-23, as well as increased accumulation of Ag-specific IFN-\u03b3\u2013producing CD8+ tissue-resident memory T (TRM) cells. The CD8+ T cell mitogen IL-15, which was increased in oxazolone-challenged skin of Sash mice during the accumulation of cutaneous TRM cells, was efficiently degraded by MCs in vitro. MCs protect from the exacerbated allergic skin inflammation induced by repeated allergen challenge, at least in part, via effects on CD8+ TRM cells. MCs may notably influence the course of chronic allergic contact dermatitis. A better understanding of their role and the underlying mechanisms may lead to better approaches for the treatment of this common, disabling, and costly condition.<\/jats:p>","DOI":"10.4049\/jimmunol.1600236","type":"journal-article","created":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T22:03:34Z","timestamp":1478124214000},"page":"4240-4246","source":"Crossref","is-referenced-by-count":45,"title":["Mast Cells Limit the Exacerbation of Chronic Allergic Contact Dermatitis in Response to Repeated Allergen Exposure"],"prefix":"10.1093","volume":"197","author":[{"given":"Vladimir-Andrey","family":"Gimenez-Rivera","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergy, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , D-10405 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Siebenhaar","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , D-10405 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , D-10405 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Siiskonen","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , D-10405 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4070-9976","authenticated-orcid":false,"given":"Martin","family":"Metz","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , D-10405 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Maurer","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , D-10405 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,12,1]]},"reference":[{"key":"2025030618355729400_r1","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s00018-011-0846-8","article-title":"Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects. Current knowledge assembled at an international workshop at BfR, Germany","volume":"69","author":"Peiser","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"2025030618355729400_r2","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/jid.2012.284","article-title":"Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis","volume":"133","author":"Honda","year":"2013","journal-title":"J. Invest. Dermatol."},{"key":"2025030618355729400_r3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1600-0625.2011.01395.x","article-title":"Extended DNFB-induced contact hypersensitivity models display characteristics of chronic inflammatory dermatoses","volume":"21","author":"R\u00f6se","year":"2012","journal-title":"Exp. Dermatol."},{"key":"2025030618355729400_r4","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.immuni.2011.07.013","article-title":"Mast cell interleukin-2 production contributes to suppression of chronic allergic dermatitis","volume":"35","author":"Hershko","year":"2011","journal-title":"Immunity"},{"key":"2025030618355729400_r5","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.4049\/jimmunol.159.5.2484","article-title":"Repeated elicitation of contact hypersensitivity induces a shift in cutaneous cytokine milieu from a T helper cell type 1 to a T helper cell type 2 profile","volume":"159","author":"Kitagaki","year":"1997","journal-title":"J. Immunol."},{"key":"2025030618355729400_r6","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.4049\/jimmunol.163.3.1265","article-title":"Distinct in vivo and in vitro cytokine profiles of draining lymph node cells in acute and chronic phases of contact hypersensitivity: importance of a type 2 cytokine-rich cutaneous milieu for the development of an early-type response in the chronic phase","volume":"163","author":"Kitagaki","year":"1999","journal-title":"J. Immunol."},{"key":"2025030618355729400_r7","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1046\/j.1365-2133.2003.05090.x","article-title":"Pattern analysis of human cutaneous mast cell populations by total body surface mapping","volume":"148","author":"Weber","year":"2003","journal-title":"Br. J. Dermatol."},{"key":"2025030618355729400_r8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jaip.2012.11.007","article-title":"Systemic contact dermatitis to ethanol","volume":"1","author":"Wolverton","year":"2013","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"2025030618355729400_r9","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.4049\/jimmunol.131.6.2687","article-title":"Defective elicitation of delayed-type hypersensitivity in W\/Wv and SI\/SId mast cell-deficient mice","volume":"131","author":"Askenase","year":"1983","journal-title":"J. Immunol."},{"key":"2025030618355729400_r10","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1084\/jem.192.10.1441","article-title":"Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2","volume":"192","author":"Biedermann","year":"2000","journal-title":"J. Exp. Med."},{"key":"2025030618355729400_r11","doi-asserted-by":"crossref","first-page":"e25538","DOI":"10.1371\/journal.pone.0025538","article-title":"Requirement of interaction between mast cells and skin dendritic cells to establish contact hypersensitivity","volume":"6","author":"Otsuka","year":"2011","journal-title":"PLoS One"},{"key":"2025030618355729400_r12","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.immuni.2011.03.028","article-title":"Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens","volume":"34","author":"Dudeck","year":"2011","journal-title":"Immunity"},{"key":"2025030618355729400_r13","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1126\/science.6494907","article-title":"Unequivocal delayed hypersensitivity in mast cell-deficient and beige mice","volume":"226","author":"Galli","year":"1984","journal-title":"Science"},{"key":"2025030618355729400_r14","doi-asserted-by":"crossref","first-page":"879","DOI":"10.4049\/jimmunol.135.2.879","article-title":"Undiminished immunologic tolerance to contact sensitivity in mast cell-deficient W\/Wv and Sl\/Sld mice","volume":"135","author":"Mekori","year":"1985","journal-title":"J. Immunol."},{"key":"2025030618355729400_r15","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/ni1503","article-title":"Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B","volume":"8","author":"Grimbaldeston","year":"2007","journal-title":"Nat. Immunol."},{"key":"2025030618355729400_r16","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.4049\/jimmunol.144.11.4121","article-title":"Roles of CD4+ and CD8+ T cells in murine contact sensitivity revealed by in vivo monoclonal antibody depletion","volume":"144","author":"Gocinski","year":"1990","journal-title":"J. Immunol."},{"key":"2025030618355729400_r17","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/978-1-60761-869-0_15","article-title":"Antiinflammatory and immunosuppressive functions of mast cells","volume":"677","author":"Kalesnikoff","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"2025030618355729400_r18","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/j.0022-202X.2005.23620.x","article-title":"Suprabasal induction of ornithine decarboxylase in adult mouse skin is sufficient to activate keratinocytes","volume":"124","author":"Lan","year":"2005","journal-title":"J. Invest. Dermatol."},{"key":"2025030618355729400_r19","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/nm.2760","article-title":"T cell homing to epithelial barriers in allergic disease","volume":"18","author":"Islam","year":"2012","journal-title":"Nat. Med."},{"key":"2025030618355729400_r20","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1038\/ni.2744","article-title":"The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin","volume":"14","author":"Mackay","year":"2013","journal-title":"Nat. Immunol."},{"key":"2025030618355729400_r21","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.4049\/jimmunol.1400003","article-title":"Cutting edge: resident memory CD8 T cells occupy frontline niches in secondary lymphoid organs","volume":"192","author":"Schenkel","year":"2014","journal-title":"J. Immunol."},{"key":"2025030618355729400_r22","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1365-2249.2006.03226.x","article-title":"Nickel, cobalt, chromium, palladium and gold induce a mixed Th1- and Th2-type cytokine response in vitro in subjects with contact allergy to the respective metals","volume":"146","author":"Minang","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"2025030618355729400_r23","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1111\/j.1523-1747.2003.12623.x","article-title":"Immunopathologic features of allergic contact dermatitis in humans: participation of plasmacytoid dendritic cells in the pathogenesis of the disease?","volume":"121","author":"Bangert","year":"2003","journal-title":"J. Invest. Dermatol."},{"key":"2025030618355729400_r24","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nm.3860","article-title":"Common clonal origin of central and resident memory T cells following skin immunization","volume":"21","author":"Gaide","year":"2015","journal-title":"Nat. Med."},{"key":"2025030618355729400_r25","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.4049\/jimmunol.175.4.2635","article-title":"Cytokine production by skin-derived mast cells: endogenous proteases are responsible for degradation of cytokines","volume":"175","author":"Zhao","year":"2005","journal-title":"J. Immunol."},{"key":"2025030618355729400_r26","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0065-2776(07)95006-3","article-title":"Mast cell proteases","volume":"95","author":"Pejler","year":"2007","journal-title":"Adv. Immunol."},{"key":"2025030618355729400_r27","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.imlet.2009.09.009","article-title":"Trans-presentation: a novel mechanism regulating IL-15 delivery and responses","volume":"127","author":"Stonier","year":"2010","journal-title":"Immunol. Lett."},{"key":"2025030618355729400_r28","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.biocel.2005.02.017","article-title":"The roles of interleukin-15 receptor alpha: trans-presentation, receptor component, or both?","volume":"37","author":"Schluns","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2025030618355729400_r29","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/nm1615","article-title":"IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities","volume":"13","author":"Orinska","year":"2007","journal-title":"Nat. Med."},{"key":"2025030618355729400_r30","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1182\/blood.V96.6.2172","article-title":"Role of common cytokine receptor gamma chain (gamma(c))- and Jak3-dependent signaling in the proliferation and survival of murine mast cells","volume":"96","author":"Suzuki","year":"2000","journal-title":"Blood"},{"key":"2025030618355729400_r31","doi-asserted-by":"crossref","first-page":"4928","DOI":"10.1002\/j.1460-2075.1996.tb00873.x","article-title":"Identification of a novel receptor\/signal transduction pathway for IL-15\/T in mast cells","volume":"15","author":"Tagaya","year":"1996","journal-title":"EMBO J."},{"key":"2025030618355729400_r32","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.1016\/j.yexcr.2009.07.019","article-title":"Intracellular IL-15 controls mast cell survival","volume":"315","author":"Mirghomizadeh","year":"2009","journal-title":"Exp. Cell Res."},{"key":"2025030618355729400_r33","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1600-0625.2010.01073.x","article-title":"Immature mast cells exhibit rolling and adhesion to endothelial cells and subsequent diapedesis triggered by E- and P-selectin, VCAM-1 and PECAM-1","volume":"19","author":"Dudeck","year":"2010","journal-title":"Exp. Dermatol."},{"key":"2025030618355729400_r34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cytogfr.2010.09.003","article-title":"Role of IL-15 in immune-mediated and infectious diseases","volume":"22","author":"Di Sabatino","year":"2011","journal-title":"Cytokine Growth Factor Rev."},{"key":"2025030618355729400_r35","doi-asserted-by":"crossref","first-page":"269rv1","DOI":"10.1126\/scitranslmed.3010641","article-title":"Resident memory T cells in human health and disease","volume":"7","author":"Clark","year":"2015","journal-title":"Sci. Transl. Med."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/197\/11\/4240\/62246591\/1600236.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/197\/11\/4240\/62246591\/1600236.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T14:17:06Z","timestamp":1741270626000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/197\/11\/4240\/7973666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,1]]},"references-count":35,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2016,12,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1600236","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726917548.793547199","asserted-by":"object"}]},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2016,12]]},"published":{"date-parts":[[2016,12,1]]}}}