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Open AccessArticle

Exacerbated Imiquimod-Induced Psoriasis-Like Skin Inflammation in IRF5-Deficient Mice

1
Department of Dermatology, the University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan
2
Department of Dermatology, St. Marianna University School of Medicine, Kanagawa 216-8511, Japan
3
Department of Dermatology, International University of Health and Welfare, Chiba 286-0124, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3681; https://doi.org/10.3390/ijms21103681
Received: 20 May 2020 / Accepted: 22 May 2020 / Published: 23 May 2020
(This article belongs to the Special Issue Therapy and Prevention of Atopic Dermatitis and Psoriasis 2020)
Interferon regulatory factors (IRFs) play diverse roles in the regulation of the innate and adaptive immune responses in various diseases. In psoriasis, IRF2 is known to be involved in pathogenesis, while studies on other IRFs are limited. In this study, we investigated the role of IRF5 in psoriasis using imiquimod-induced psoriasis-like dermatitis. Although IRF5 is known to play a critical role in the induction of proinflammatory cytokines by immune cells, such as dendritic cells (DCs), macrophages, and monocytes, IRF5 deficiency unexpectedly exacerbated psoriasiform skin inflammation. The interferon-α and tumor necrosis factor-α mRNA expression levels were decreased, while levels of Th17 cytokines including IL-17, IL-22, and IL-23 were increased in IRF5-deficient mice. Furthermore, IL-23 expression in DCs from IRF5-deficient mice was upregulated both in steady state and after toll-like receptor 7/8 agonist stimulation. Importantly, the expression of IRF4, which is also important for the IL-23 production in DCs, was augmented in DCs from IRF5-deficient mice. Taken together, our results suggest that IRF5 deficiency induces the upregulation of IRF4 in DCs followed by augmented IL-23 production, resulting in the amplification of Th17 responses and the exacerbation of imiquimod-induced psoriasis-like skin inflammation. The regulation of IRF4 or IRF5 expression may be a novel therapeutic approach to psoriasis. View Full-Text
Keywords: interferon regulatory factor 5; psoriasis; imiquimod; IL-23; dendritic cells; interferon regulatory factor 4 interferon regulatory factor 5; psoriasis; imiquimod; IL-23; dendritic cells; interferon regulatory factor 4
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Nakao, M.; Miyagaki, T.; Sugaya, M.; Sato, S. Exacerbated Imiquimod-Induced Psoriasis-Like Skin Inflammation in IRF5-Deficient Mice. Int. J. Mol. Sci. 2020, 21, 3681.

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