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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Bibliographic Details
Published in:International journal of molecular sciences 2022-05, Vol.23 (10), p.5726
Main Authors: 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
Format: Article
Language:English
Subjects:
Abdomen
Ablation
Amyloid
Amyloidosis
Arthritis
CD4 antigen
CD8 antigen
Cytokines
Deposition
Dermatitis
Disease
Inflammation
Inflammatory bowel diseases
Janus kinase
Kinases
Liver
Lymphatic system
Lymphocytes
Lymphocytes T
Pathophysiology
Proteins
Psoriasis
Rheumatoid arthritis
Skin
Skin diseases
Spleen
Tumor necrosis factor-TNF
Veins & arteries
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23105726