{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:30:55Z","timestamp":1790857855546,"version":"4.1.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,8,20]]},"abstract":"<jats:p>Atopic dermatitis (AD) is a pruritic inflammatory skin disease. Because IL-18 directly stimulates T cells and mast cells to release AD-associated molecules, Th2 cytokines, and histamine, we investigated the capacity of IL-18 to induce AD-like inflammatory skin disease by analyzing KIL-18Tg and KCASP1Tg, which skin-specifically overexpress IL-18 and caspase-1, respectively. They spontaneously developed relapsing dermatitis with mastocytosis and Th2 cytokine accumulation accompanied by systemic elevation of IgE and histamine. Stat6-deficient KCASP1Tg displayed undetectable levels of IgE but manifested the same degree of cutaneous changes, whereas IL-18-deficient KCASP1Tg evaded the dermatitis, suggesting that IL-18 causes the skin changes in the absence of IgE\/stat6. KIL-18Tg and IL-1-deficient KCASP1Tg took longer to display the lesion than KCASP1Tg. Thus, AD-like inflammation is initiated by overrelease of IL-18 and accelerated by IL-1. Our present study might provide insight into understanding the pathogenesis of and establishing therapeutics for chronic inflammatory skin diseases including AD.<\/jats:p>","DOI":"10.1073\/pnas.152337799","type":"journal-article","created":{"date-parts":[[2002,9,30]],"date-time":"2002-09-30T12:42:53Z","timestamp":1033389773000},"page":"11340-11345","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":222,"title":["IL-18 contributes to the spontaneous development of atopic dermatitis-like inflammatory skin lesion independently of IgE\/stat6 under specific pathogen-free conditions"],"prefix":"10.1073","volume":"99","author":[{"given":"Hiroshi","family":"Konishi","sequence":"first","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Tsutsui","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Murakami","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizue","family":"Yumikura-Futatsugi","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei-ichi","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohichiro","family":"Iwakura","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Takeda","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Akira","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Mizutani","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Biochemistry, and Institute of Laboratory Animals, Mie University School of Medicine, Tsu 514-8507, Japan; Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Host Defenses, Research Institute for Microbial Diseases, Suita 565-0871, Japan; and Core Research for Evolutional Science and Technology,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,7,31]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(95)70049-8"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)12082-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198707023170106"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/339064a0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60496-4"},{"key":"e_1_3_3_6_2","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.4049\/jimmunol.155.4.1796","volume":"155","author":"Okayama Y.","year":"1995","unstructured":"Okayama Y., Petit-Frere, C., Kassel, O., Semper, A., Quint, D., Tunon-de-Lara, M. J., Bradding, P., Hogate, S. T. & Church, M. K. (1995) J. Immunol.155,1796-1808.7543533","journal-title":"J. Immunol."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.14.8080"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.1.43"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.24.13962"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.423"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/378088a0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"crossref","first-page":"3400","DOI":"10.4049\/jimmunol.161.7.3400","volume":"161","author":"Yoshimoto T.","year":"1998","unstructured":"Yoshimoto T., Takeda, K., Tanaka, T., Ohkusu, K., Kashiwamura, S., Okamura, H., Akira, S. & Nakanishi, K. (1998) J. Immunol.161,3400-3407.9759857","journal-title":"J. Immunol."},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199902)29:02<548::AID-IMMU548>3.0.CO;2-Z"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/77811"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.12.7014"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115067"},{"key":"e_1_3_3_17_2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.4049\/jimmunol.159.1.298","volume":"159","author":"Stoll S.","year":"1997","unstructured":"Stoll S., Muller, G., Kurimoto, M., Saloga, J., Tanimoto, T., Yamauchi, H., Okamura, H., Knop, J. & Enk, A. H. (1997) J. Immunol.159,298-302.9200466","journal-title":"J. Immunol."},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.6.2095.bloodjournal8762095"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5297.206"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020506300324"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.4.2651"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80111-9"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.997"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1159\/000060597"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300908"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.9.1463"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/380627a0"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80543-9"},{"key":"e_1_3_3_29_2","doi-asserted-by":"crossref","first-page":"3967","DOI":"10.4049\/jimmunol.157.9.3967","volume":"157","author":"Tsutsui H.","year":"1996","unstructured":"Tsutsui H., Nakanishi, K., Matsui, K., Higashino, K., Okamura, H., Miyazawa, Y. & Kaneda, K. (1996) J. Immunol.157,3967-3973.8892629","journal-title":"J. Immunol."},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.7.2101"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/357080a0"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(96)10030-X"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1978.tb01462.x"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12331164"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.15.5654"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.07.040189.000423"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00440-3"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90540-7"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119255"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.5.2879"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200104)31:4<1010::AID-IMMU1010>3.0.CO;2-8"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198007033030109"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/90609"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5928"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.152337799","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T14:45:09Z","timestamp":1682347509000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.152337799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,7,31]]},"references-count":44,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2002,8,20]]}},"alternative-id":["10.1073\/pnas.152337799"],"URL":"https:\/\/doi.org\/10.1073\/pnas.152337799","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,7,31]]},"assertion":[{"value":"2002-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-06-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-07-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}