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Affiliation |
Faculty of Medicine School of Medicine Department of Infectious Diseases, Immunology |
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Assistant Professor |
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Related SDGs |
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Fukaya Tomohiro
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Papers 【 display / non-display 】
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Clec4A4 Acts As A Negative Immune Checkpoint Regulator to Suppress Antitumor Immunity. Reviewed
Uto T, Fukaya T, Mitoma S, Nishikawa Y, Tominaga M, Choijookhuu N, Hishikawa Y, Sato K
Cancer immunology research 11 ( 9 ) 1266 - 1279 2023.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Cancer Immunology Research
Clec4A4 is a C-Type lectin receptor (CLR) exclusively expressed on murine conventional dendritic cells (cDC) to regulate their activation status. However, the functional role of murine Clec4A4 (mClec4A4) in antitumor immunity remains unclear. Here, we show that mClec4A4 serves as a negative immune checkpoint regulator to impair antitumor immune responses. Deficiency of mClec4A4 lead to a reduction in tumor development, accompanied by enhanced antitumor immune responses and amelioration of the immunosuppressive tumor microenvironment (TME) mediated through the enforced activation of cDCs in tumor-bearing mice. Furthermore, antagonistic mAb to human CLEC4A (hCLEC4A), which is the functional orthologue of mClec4A4, exerted protection against established tumors without any apparent signs of immunerelated adverse events in hCLEC4A-Transgenic mice. Thus, our findings highlight the critical role of mClec4A4 expressed on cDCs as a negative immune checkpoint molecule in the control of tumor progression and provide support for hCLEC4A as a potential target for immune checkpoint blockade in tumor immunotherapy.
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Fukaya T., Uto T., Mitoma S., Takagi H., Nishikawa Y., Tominaga M., Choijookhuu N., Hishikawa Y., Sato K.
Cell Reports 42 ( 5 ) 112431 2023.5
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Cell Reports
While dysbiosis in the gut is implicated in the impaired induction of oral tolerance generated in mesenteric lymph nodes (MesLNs), how dysbiosis affects this process remains unclear. Here, we describe that antibiotic-driven gut dysbiosis causes the dysfunction of CD11c+CD103+ conventional dendritic cells (cDCs) in MesLNs, preventing the establishment of oral tolerance. Deficiency of CD11c+CD103+ cDCs abrogates the generation of regulatory T cells in MesLNs to establish oral tolerance. Antibiotic treatment triggers the intestinal dysbiosis linked to the impaired generation of colony-stimulating factor 2 (Csf2)-producing group 3 innate lymphoid cells (ILC3s) for regulating the tolerogenesis of CD11c+CD103+ cDCs and the reduced expression of tumor necrosis factor (TNF)-like ligand 1A (TL1A) on CD11c+CD103+ cDCs for generating Csf2-producing ILC3s. Thus, antibiotic-driven intestinal dysbiosis leads to the breakdown of crosstalk between CD11c+CD103+ cDCs and ILC3s for maintaining the tolerogenesis of CD11c+CD103+ cDCs in MesLNs, responsible for the failed establishment of oral tolerance.
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TYK2 is essential for the therapeutic effect of IFN-α in Jak2V617F-induced murine myeloproliferative neoplasms Reviewed
Yuki Tahira , Kotaro Shide , Takuro Kameda , Taisuke Uchida , Ayako Kamiunten , Keiichi Akizuki , Yoko Kubuki , Masayoshi Karasawa , Ryoma Ikeda , Kengo Matsumoto , Jie Bai , Minoru Terashima , Koji Kato , Tomofumi Uto , Tomohiro Fukaya , Shuya Mitoma , Katsuaki Sato , Yudai Uehira , Hiroaki Ueno , Goro Sashida , Hideki Yamaguchi , Kazuya Shimoda
Blood Neoplasia 2 ( 3 ) 100087 2025.8
Language：English Publishing type：Research paper (scientific journal)
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Selectivity of bovine interleukin-2 mutein stimulation on bovine peripheral blood mononuclear cells Reviewed
MITOMA Shuya, UTO Tomofumi, FUKAYA Tomohiro, TOMINAGA Moe, SEKIGUCHI Satoshi, SATO Katsuaki, NORIMINE Junzo
Journal of Veterinary Medical Science advpub ( 0 ) 2025.5
Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE SOCIETY OF VETERINARY SCIENCE
DOI： 10.1292/jvms.24-0470
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Crucial role of dendritic cells in the generation of anti-tumor T-cell responses and immunogenic tumor microenvironment to suppress tumor development Reviewed International coauthorship
Tominaga M., Uto T., Fukaya T., Mitoma S., Riethmacher D., Umekita K., Yamashita Y., Sato K.
Frontiers in Immunology 15 1200461 2024.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers in Immunology
Books 【 display / non-display 】
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Current Topics in Microbiology and Immunology
Sato, K. Uto, T., Fukaya, T., and Takagi, H.（ Role： Joint author , Regulatory dendritic cells）
Springer Publishing 2017.9
Language：English Book type：Scholarly book
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Methods in Molecular Biology
Fukaya, T., Takagi, H., Uto, T, Arimura, K., and Sato, K.（ Role： Joint author , Analysis of DC functions using CD205-DTR knock-in mice）
Springer Publishing 2016.5
Language：English Book type：Scholarly book
MISC 【 display / non-display 】
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樹状細胞のはたらき⑧樹状細胞を標的とした免疫チェックポイント阻害療法 Invited
宇都倫史•深谷知宏•三苫修也•佐藤克明
Veterinary Immunology for Practitioners ( 37 ) 26 - 31 2025.1
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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樹状細胞のはたらき⑦がん免疫応答における通常型樹状細胞の役割 Invited
宇都倫史•深谷知宏•三苫修也•佐藤克明
Veterinary Immunology for Practitioners ( 36 ) 46 - 51 2024.10
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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樹状細胞のはたらき⑥アレルギー疾患に対する舌下免疫療法の防御効果における樹状細胞の役割 Invited
深谷知宏•宇都倫史•三苫修也•佐藤克明
Veterinary Immunology for Practitioners ( 35 ) 44 - 49 2024.7
Authorship：Lead author Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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樹状細胞のはたらき⑤幼若期での抗生剤服用による消化管細菌叢異常に基づく経口免疫寛容の破綻における通常型樹状細胞の役割 Invited
深谷知宏•宇都倫史•三苫修也•佐藤克明
Veterinary Immunology for Practitioners ( 34 ) 15 - 21 2024.4
Authorship：Lead author Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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樹状細胞のはたらき④経口免疫寛容の誘導における形質細胞様樹状細胞の役割 Invited
深谷知宏•宇都倫史•三苫修也•佐藤克明
Veterinary Immunology for Practitioners ( 33 ) 15 - 19 2024.1
Authorship：Lead author Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
Presentations 【 display / non-display 】
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樹状細胞による免疫寛容の誘導に基づくアレルギー制御 Invited
深谷知宏, 佐藤克明
日本食品免疫学会21回学術大会 2025.10.2
Event date： 2025.10.2 - 2025.10.3
Language：Japanese Presentation type：Symposium, workshop panel (nominated)
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Clec4A4/CLEC4A acts as a negative immune checkpoint regulator to suppress anti-tumor immunity
宇都倫史、深谷知宏、三笘修也、冨永萌、佐藤克明
第53回日本免疫学会総会 2024.12
Event date： 2024.12
Language：English Presentation type：Poster presentation
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高度免疫不全マウスを用いた牛伝染性リンパ腫担がんマウスモデル及び牛免疫細胞移植マウスモデルの作製と有用性の検討
三苫修也、宇都倫史、深谷知宏、冨永萌、関口敏、佐藤克明
第167回日本獣医学会学術集会 2024.11
Event date： 2024.11
Language：Japanese Presentation type：Poster presentation
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Gut dysbiosis abrogates the establishment of oral tolerance mediated through dysfunction of mucosal dendritic cells
深谷知宏、宇都倫史、三笘修也、冨永萌、佐藤克明
第52回日本免疫学会総会 2024.1.17
Event date： 2024.1.17 - 2024.1.19
Language：English Presentation type：Poster presentation
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Selective cell stimulation with bovine interleukin-2 mutein and the distribution of bovine CD122 on the peripheral lymphocytes
三笘修也、宇都倫史、深谷知宏、冨永萌、佐藤克明
第52回日本免疫学会総会 2024.1.17
Event date： 2024.1.17 - 2024.1.19
Language：English Presentation type：Poster presentation
Awards 【 display / non-display 】
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第51回日本免疫学会学術集会 ベストポスター賞
2022.12 日本免疫学会 Gut dysbiosis abrogates the establishment of oral tolerance through the dysregulation of the crosstalk between CD103 + conventional dendritic cells and innate lymphoid cells in mesenteric lymph nodes
深谷知宏
Award type：Award from Japanese society, conference, symposium, etc.
Grant-in-Aid for Scientific Research 【 display / non-display 】
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形質細胞様樹状細胞の機能制御分子を標的とした新規免疫チェックポイント阻害剤の開発
Grant number：23K06768 2023.04 - 2026.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(C)
Authorship：Principal investigator
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IL-22結合タンパクによる皮膚炎症慢性化に対する制御機構の解明
Grant number：17K15732 2017.04 - 2020.03
科学研究費補助金 若手研究(B)
Authorship：Principal investigator
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CD4陽性通常型樹状細胞による自己免疫疾患の制御機構の解明
Grant number：26860337 2014.04 - 2017.03
科学研究費補助金 若手研究(B)
Authorship：Principal investigator
CD4陽性通常型樹状細胞による自己免疫疾患の制御機構の解明