{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T14:15:11Z","timestamp":1769350511504,"version":"3.49.0"},"reference-count":29,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eli Lilly and Company","award":["J17011L017"],"award-info":[{"award-number":["J17011L017"]}]},{"name":"Eli Lilly and Company","award":["1166"],"award-info":[{"award-number":["1166"]}]},{"name":"Eli Lilly and Company","award":["SPJS20190717002"],"award-info":[{"award-number":["SPJS20190717002"]}]},{"name":"Eli Lilly and Company","award":["2020"],"award-info":[{"award-number":["2020"]}]},{"name":"AbbVie GK","award":["J17011L017"],"award-info":[{"award-number":["J17011L017"]}]},{"name":"AbbVie GK","award":["1166"],"award-info":[{"award-number":["1166"]}]},{"name":"AbbVie GK","award":["SPJS20190717002"],"award-info":[{"award-number":["SPJS20190717002"]}]},{"name":"AbbVie GK","award":["2020"],"award-info":[{"award-number":["2020"]}]},{"name":"Sun Pharma","award":["J17011L017"],"award-info":[{"award-number":["J17011L017"]}]},{"name":"Sun Pharma","award":["1166"],"award-info":[{"award-number":["1166"]}]},{"name":"Sun Pharma","award":["SPJS20190717002"],"award-info":[{"award-number":["SPJS20190717002"]}]},{"name":"Sun Pharma","award":["2020"],"award-info":[{"award-number":["2020"]}]},{"name":"Maruho Takagi Dermatology Foundation","award":["J17011L017"],"award-info":[{"award-number":["J17011L017"]}]},{"name":"Maruho Takagi Dermatology Foundation","award":["1166"],"award-info":[{"award-number":["1166"]}]},{"name":"Maruho Takagi Dermatology Foundation","award":["SPJS20190717002"],"award-info":[{"award-number":["SPJS20190717002"]}]},{"name":"Maruho Takagi Dermatology Foundation","award":["2020"],"award-info":[{"award-number":["2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic amyloidosis is recognized as a serious complication of rheumatoid arthritis or inflammatory bowel disease, but also of inflammatory skin disease. However, the detailed molecular mechanism of amyloidosis associated with cutaneous inflammation remains unclear, and therapeutic approaches are limited. Here, we investigated the pathophysiology of amyloidosis secondary to cutaneous inflammation and the therapeutic effects of Janus kinase (JAK) inhibitors by examining a mouse model of spontaneous dermatitis (KCASP1Tg mice). Moreover, KCASP1Tg mice were crossed with interleukin-17A (IL-17A) knockout mice to generate IL-17A-\/KCASP1Tg and examine the role of IL-17A in amyloidosis under cutaneous inflammation. KCASP1Tg mice showed severe amyloid deposition in the liver and spleen. Increased serum-neutral fat levels and decreased lymphocyte production were observed in the spleen. Overproduction of amyloidosis was partially ameliorated by the administration of JAK inhibitors and was further improved in IL-17A-\/KCASP1Tg mice. IL-17A-producing cells included CD4, gamma delta, and CD8 T cells. In summary, our results from the analysis of a mouse model of dermatitis revealed that skin-derived inflammatory cytokines can induce amyloid deposition in the liver and spleen, and that the administration of JAK inhibitors and, even more, IL-17A ablation, reduced amyloidosis. This study demonstrates that active control of skin inflammation is essential to prevent internal organ amyloidosis.<\/jats:p>","DOI":"10.3390\/ijms23105726","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T13:56:12Z","timestamp":1653054972000},"page":"5726","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["IL-17A Is the Critical Cytokine for Liver and Spleen Amyloidosis in Inflammatory Skin Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Shohei","family":"Iida","sequence":"first","affiliation":[{"name":"Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehisa","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiyasu","family":"Momose","sequence":"additional","affiliation":[{"name":"Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Ichishi","sequence":"additional","affiliation":[{"name":"Department of Oncologic Pathology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5171-4909","authenticated-orcid":false,"given":"Kento","family":"Mizutani","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6114-0830","authenticated-orcid":false,"given":"Yoshiaki","family":"Matsushima","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai","family":"Umaoka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1560-6067","authenticated-orcid":false,"given":"Makoto","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Habe","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshifumi","family":"Hirokawa","sequence":"additional","affiliation":[{"name":"Department of Oncologic Pathology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Oncologic Pathology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9934-5775","authenticated-orcid":false,"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[{"name":"Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Miyahara","sequence":"additional","affiliation":[{"name":"Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3169-5717","authenticated-orcid":false,"given":"Yasutomo","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan"},{"name":"Imai Dermatology Pediatric Dermatology Allergology, 5-1-1 Ebie, Fukushima, Osaka 553-0001, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichi","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Mie 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