Characterization of novel anti-IL-26 neutralizing monoclonal antibodies for the treatment of inflammatory diseases including psoriasis
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- Ryo Hatano
- Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan
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- Takumi Itoh
- Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan
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- Haruna Otsuka
- Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan
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- Sayo Okamoto
- Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan
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- Eriko Komiya
- Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan
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- Satoshi Iwata
- Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan
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- Thomas M. Aune
- Department of Medicine, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
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- Nam H. Dang
- Division of Hematology/Oncology, University of Florida, Gainesville, FL, USA
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- Kyoko Kuwahara-Arai
- Department of Microbiology, Juntendo University School of Medicine, Tokyo, Japan
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- Kei Ohnuma
- Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan
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- Chikao Morimoto
- Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan
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説明
Interleukin (IL)-26, known as a Th17 cytokine, acts on various cell types and has multiple biological functions. Although its precise role still remains to be elucidated, IL-26 is suggested to be associated with the pathology of diverse chronic inflammatory diseases such as psoriasis, inflammatory bowel diseases and rheumatoid arthritis. To develop novel neutralizing anti-human IL-26 monoclonal antibodies (mAbs) for therapeutic use in the clinical setting, we immunized mice with human IL-26 protein. Hybridomas producing anti-IL-26 mAbs were screened for various in vitro functional assays, STAT3 phosphorylation and antibiotic assays. Although the IL-20RA/IL-10RB heterodimer is generally believed to be the IL-26 receptor, our data strongly suggest that both IL-20RA-dependent and -independent pathways are involved in IL-26-mediated stimulation. We also investigated the potential therapeutic effect of anti-IL-26 mAbs in the imiquimod-induced psoriasis-like murine model using human IL-26 transgenic mice. These screening methods enabled us to develop novel neutralizing anti-human IL-26 mAbs. Importantly, administration of IL-26-neutralizing mAb did not have an effect on the antimicrobial activity of IL-26. Taken together, our data strongly suggest that our newly developed anti-human IL-26 mAb is a potential therapeutic agent for the treatment of diverse chronic inflammatory diseases including psoriasis.
収録刊行物
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- mAbs
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mAbs 11 (8), 1428-1442, 2019-08-18
Informa UK Limited
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詳細情報 詳細情報について
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- CRID
- 1360849944149884160
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- ISSN
- 19420870
- 19420862
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE