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IL-17A Is the Critical Cytokine for Liver and Spleen Amyloidosis in Inflammatory Skin Disease

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 l...

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Autores principales: Iida, Shohei, Nakanishi, Takehisa, Momose, Fumiyasu, Ichishi, Masako, Mizutani, Kento, Matsushima, Yoshiaki, Umaoka, Ai, Kondo, Makoto, Habe, Koji, Hirokawa, Yoshifumi, Watanabe, Masatoshi, Iwakura, Yoichiro, Miyahara, Yoshihiro, Imai, Yasutomo, Yamanaka, Keiichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147816/
https://www.ncbi.nlm.nih.gov/pubmed/35628531
http://dx.doi.org/10.3390/ijms23105726
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author Iida, Shohei
Nakanishi, Takehisa
Momose, Fumiyasu
Ichishi, Masako
Mizutani, Kento
Matsushima, Yoshiaki
Umaoka, Ai
Kondo, Makoto
Habe, Koji
Hirokawa, Yoshifumi
Watanabe, Masatoshi
Iwakura, Yoichiro
Miyahara, Yoshihiro
Imai, Yasutomo
Yamanaka, Keiichi
author_facet Iida, Shohei
Nakanishi, Takehisa
Momose, Fumiyasu
Ichishi, Masako
Mizutani, Kento
Matsushima, Yoshiaki
Umaoka, Ai
Kondo, Makoto
Habe, Koji
Hirokawa, Yoshifumi
Watanabe, Masatoshi
Iwakura, Yoichiro
Miyahara, Yoshihiro
Imai, Yasutomo
Yamanaka, Keiichi
author_sort Iida, Shohei
collection PubMed
description 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.
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spelling pubmed-91478162022-05-29 IL-17A Is the Critical Cytokine for Liver and Spleen Amyloidosis in Inflammatory Skin Disease Iida, Shohei Nakanishi, Takehisa Momose, Fumiyasu Ichishi, Masako Mizutani, Kento Matsushima, Yoshiaki Umaoka, Ai Kondo, Makoto Habe, Koji Hirokawa, Yoshifumi Watanabe, Masatoshi Iwakura, Yoichiro Miyahara, Yoshihiro Imai, Yasutomo Yamanaka, Keiichi Int J Mol Sci Article 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. MDPI 2022-05-20 /pmc/articles/PMC9147816/ /pubmed/35628531 http://dx.doi.org/10.3390/ijms23105726 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Iida, Shohei
Nakanishi, Takehisa
Momose, Fumiyasu
Ichishi, Masako
Mizutani, Kento
Matsushima, Yoshiaki
Umaoka, Ai
Kondo, Makoto
Habe, Koji
Hirokawa, Yoshifumi
Watanabe, Masatoshi
Iwakura, Yoichiro
Miyahara, Yoshihiro
Imai, Yasutomo
Yamanaka, Keiichi
IL-17A Is the Critical Cytokine for Liver and Spleen Amyloidosis in Inflammatory Skin Disease
title IL-17A Is the Critical Cytokine for Liver and Spleen Amyloidosis in Inflammatory Skin Disease
title_full IL-17A Is the Critical Cytokine for Liver and Spleen Amyloidosis in Inflammatory Skin Disease
title_fullStr IL-17A Is the Critical Cytokine for Liver and Spleen Amyloidosis in Inflammatory Skin Disease
title_full_unstemmed IL-17A Is the Critical Cytokine for Liver and Spleen Amyloidosis in Inflammatory Skin Disease
title_short IL-17A Is the Critical Cytokine for Liver and Spleen Amyloidosis in Inflammatory Skin Disease
title_sort il-17a is the critical cytokine for liver and spleen amyloidosis in inflammatory skin disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147816/
https://www.ncbi.nlm.nih.gov/pubmed/35628531
http://dx.doi.org/10.3390/ijms23105726
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