{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:53:05Z","timestamp":1760237585133,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T00:00:00Z","timestamp":1591315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI Grant-in-Aid for Young Scientists B 16K20443, and Grant-in-Aid for Scientific Research C 19K10371."],"award-info":[{"award-number":["KAKENHI Grant-in-Aid for Young Scientists B 16K20443, and Grant-in-Aid for Scientific Research C 19K10371."]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metal allergy is usually diagnosed by patch testing, however, the results do not necessarily reflect the clinical symptoms because of cross-reactivity between different metals. In this study, we established the novel mouse model of cross-reactive metal allergy, and aimed to elucidate the immune response in terms of T-cell receptor repertoire. This model was classified into two groups: the sensitization to nickel and challenge with palladium group, and the sensitization to chromium and challenge with palladium group. This model developed spongiotic edema with intra- and peri-epithelial infiltration of CD4+ T cells in the inflamed skin that resembles human contact dermatitis. Using T cell receptor analysis, we detected a high proportion of T cells bearing Trav8d-1-Traj49 and Trav5-1-Traj37 in the Ni- and Cr-sensitized Pd-challenged mice. Furthermore, mucosal-associated invariant T cells and invariant natural killer T cells were also detected. Our results indicated that T cells bearing Trav8d-1-Traj49 and Trav5-1-Traj37 induced the development of palladium-cross reactive allergy, and that mucosal-associated invariant T and invariant natural killer T cells were also involved in the cross-reactivity between different metals.<\/jats:p>","DOI":"10.3390\/ijms21114061","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T05:16:14Z","timestamp":1591679774000},"page":"4061","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cross-Reactivity of Palladium in a Murine Model of Metal-induced Allergic Contact Dermatitis"],"prefix":"10.3390","volume":"21","author":[{"given":"Hiroaki","family":"Shigematsu","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Toshiba Rinkan Hospital, 7-9-1 Kamitsuruma, Minami-ku, Sagamihara, Kanagawa 252-0385, Japan"},{"name":"Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan"},{"name":"Department of Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Kumagai","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan"},{"name":"Department of Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoaki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan"},{"name":"Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4608-1347","authenticated-orcid":false,"given":"Takanori","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan"},{"name":"Department of Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Saku General Hospital, 197, Usuda, Saku, Nagano 394-0301, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasunari","family":"Nakasone","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Nagano Matsushiro General Hospital, 183, Matsushiro, Nagano 381-1231 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Nasu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan"},{"name":"Department of Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takamasa","family":"Yoshizawa","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan"},{"name":"Department of Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruno","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan"},{"name":"Department of Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7324-8574","authenticated-orcid":false,"given":"Takahiro","family":"Mori","sequence":"additional","affiliation":[{"name":"Departments of Clinical Oncology and Gastroenterological Surgery, National Hospital Organization Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiki","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuji","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,5]]},"reference":[{"key":"ref_1","first-page":"653","article-title":"Immunology of metal allergies","volume":"13","author":"Schmidt","year":"2015","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1600-0536.2009.01524.x","article-title":"Investigation of contact allergy to dental metals in 206 patients","volume":"60","author":"Raap","year":"2009","journal-title":"Contact Dermat."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1600-0536.2011.01878.x","article-title":"Metal allergen of the 21st century--a review on exposure, epidemiology and clinical manifestations of palladium allergy","volume":"64","author":"Faurschou","year":"2011","journal-title":"Contact Dermat."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yoshihisa, Y., and Shimizu, T. (2012). Metal allergy and systemic contact dermatitis: An overview. Dermatol. Res. Pract., 749561.","DOI":"10.1155\/2012\/749561"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1302\/0301-620X.94B8.28135","article-title":"Metal hypersensitivity testing in patients undergoing joint replacement: A systematic review","volume":"94","author":"Granchi","year":"2012","journal-title":"J. Bone Joint Surg. Br."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1600-0536.1997.tb02435.x","article-title":"National rates and regional differences in sensitization to allergens of the standard series. Population-adjusted frequencies of sensitization (PAFS) in 40,000 patients from a multicenter study (IVDK)","volume":"37","author":"Schnuch","year":"1997","journal-title":"Contact Dermat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1600-0536.2009.01650.x","article-title":"Nickel, cobalt and chromate sensitization and occupation","volume":"62","author":"Rui","year":"2010","journal-title":"Contact Dermat."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kobayashi, H., Kumagai, K., Eguchi, T., Shigematsu, H., Kitaura, K., Kawano, M., Horikawa, T., Suzuki, S., Matsutani, T., and Ogasawara, K. (2013). Characterization of T cell receptors of Th1 cells infiltrating inflamed skin of a novel murine model of palladium-induced metal allergy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076385"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.cellimm.2013.07.010","article-title":"Accumulation of invariant NKT cells into inflamed skin in a novel murine model of nickel allergy","volume":"284","author":"Eguchi","year":"2013","journal-title":"Cell. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shigematsu, H., Kumagai, K., Kobayashi, H., Eguchi, T., Kitaura, K., Suzuki, S., Horikawa, T., Matsutani, T., Ogasawara, K., and Hamada, Y. (2014). Accumulation of metal-specific T cells in inflamed skin in a novel murine model of chromium-induced allergic contact dermatitis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085983"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1067\/mjd.2000.107235","article-title":"Contact sensitivity to nickel and other metals in jewelry reactors","volume":"43","author":"Gawkrodger","year":"2000","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.0105-1873.2005.00577.x","article-title":"Cross-reactivity between nickel and palladium demonstrated by systemic administration of nickel","volume":"53","author":"Bruze","year":"2005","journal-title":"Contact Dermat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/j.1600-0536.2007.01144.x","article-title":"Occupational allergic contact dermatitis to platinum, palladium, and gold","volume":"57","author":"Watsky","year":"2007","journal-title":"Contact Dermat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1002\/eji.1830251216","article-title":"Characterization of processing requirements and metal cross-reactivities in T cell clones from patients with allergic contact dermatitis to nickel","volume":"25","author":"Moulon","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3389\/fimmu.2017.00389","article-title":"Different Somatic Hypermutation Levels among Antibody Subclasses Disclosed by a New Next-Generation Sequencing-Based Antibody Repertoire Analysis","volume":"3","author":"Kitaura","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.3389\/fimmu.2017.01206","article-title":"Natural Killer T Cell-Targeted Immunotherapy Mediating Long-term Memory Responses and Strong Antitumor Activity","volume":"25","author":"Dashtsoodol","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Martin, E., Treiner, E., Duban, L., Guerri, L., Laude, H., Toly, C., Premel, V., Devys, A., Moura, I.C., and Tilloy, F. (2009). Stepwise development of MAIT cells in mouse and human. PLoS Biol., 10.","DOI":"10.1371\/journal.pbio.1000054"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/j.1600-0536.1996.tb02389.x","article-title":"Multiple sensitivities to transition metals: The nickel palladium reactions","volume":"35","author":"Santucci","year":"1996","journal-title":"Contact Dermat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/1523-1747.ep12313366","article-title":"Cross-reactivity of human nickel-reactive T-lymphocyte clones with copper and palladium","volume":"105","author":"Pistoor","year":"1995","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1600-0625.1995.tb00246.x","article-title":"Interaction of palladium ions with the skin","volume":"4","author":"Santucci","year":"1995","journal-title":"Exp. Dermatol."},{"key":"ref_21","first-page":"131","article-title":"The role of CD4+ and CD8+ T cells in contact hypersensitivity and allergic contact dermatitis","volume":"14","author":"Berard","year":"2004","journal-title":"Eur. J. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3109\/15569520903496746","article-title":"The role of CD4+ T cells in the induction of contact hypersensitivity to mercury in a murine model","volume":"29","author":"Sumiwi","year":"2010","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/nnano.2016.88","article-title":"Metal nanoparticles in the presence of lipopolysaccharides trigger the onset of metal allergy in mice","volume":"11","author":"Hirai","year":"2016","journal-title":"Nat. Nanotechnol."},{"key":"ref_24","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":"ref_25","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":"ref_26","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1172\/JCI9199","article-title":"T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis","volume":"106","author":"Trautmann","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ajoms.2017.08.001","article-title":"Possible involvement of invariant natural killer T cells and mucosal-associated invariant T cells in a murine model of titanium allergy","volume":"30","author":"Kumagai","year":"2018","journal-title":"J. Oral Maxillofac. Surg. Med. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1084\/jem.178.1.1","article-title":"Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8- alpha\/beta T cells demonstrates preferential use of several V beta genes and an invariant TCR alpha chain","volume":"178","author":"Porcelli","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1084\/jem.189.12.1907","article-title":"An invariant T cell receptor alpha chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted alpha\/beta T cell subpopulation in mammals","volume":"189","author":"Tilloy","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/nature01433","article-title":"Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1","volume":"422","author":"Treiner","year":"2003","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/art.33314","article-title":"Mucosal-associated invariant T cells promote inflammation and exacerbate disease in murine models of arthritis","volume":"64","author":"Chiba","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kumagai, K., Horikawa, T., Shigematsu, H., Matsubara, R., Kitaura, K., Eguchi, T., Kobayashi, H., Nakasone, Y., Sato, K., and Yamada, H. (2016). Possible Immune Regulation of Natural Killer T Cells in a Murine Model of Metal Ion-Induced Allergic Contact Dermatitis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010087"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S0959-440X(94)90317-4","article-title":"Cumulative index to subjects","volume":"4","author":"Jernigan","year":"1994","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_34","first-page":"1","article-title":"Structural Aspects of metal liganding to functional groups in proteins","volume":"42","author":"Glusker","year":"1991","journal-title":"Adv. Prot. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1538\/expanim.60.481","article-title":"Effect of three types of mixed anesthetic agents alternate to ketamine in mice","volume":"60","author":"Kawai","year":"2011","journal-title":"Exp. Anim."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/11\/4061\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:36:08Z","timestamp":1760175368000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/11\/4061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,5]]},"references-count":35,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["ijms21114061"],"URL":"https:\/\/doi.org\/10.3390\/ijms21114061","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2020,6,5]]}}}