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医学部 医学科 感染症学講座免疫学分野 |
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Mitoma S., Carr B.V., Harvey Y., Moffat K., Sekiguchi S., Charleston B., Norimine J., Seago J.
Immunology 164 ( 2 ) 266 - 278 2021年10月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Immunology
Foot-and-mouth disease (FMD) is a highly contagious, economically devastating disease of cloven-hooved animals. The development of long-lasting effective FMD vaccines would greatly benefit the global FMD control programme. Deep analysis of adaptive immunity in cattle vaccinated against FMD is technically challenging due to the lack of species-specific tools. In this study, we aimed to identify CD4+ T-cell epitopes in the FMD virus (FMDV) capsid and to phenotype the CD4+ T cells that recognize them using bovine major histocompatibility complex (BoLA) class II tetramer. A BoLA class II tetramer based on the DRA/DRB3*020:02 allele and FMDV antigen-stimulated PBMCs from bovine vaccinates were used to successfully identify four epitopes in the FMDV capsid, three of which have not been previously reported; two epitopes were identified in the structural protein VP1, one in VP3 and one in VP4. Specificity of the three novel epitopes was confirmed by proliferation assay. All epitope-expanded T-cell populations produced IFN-γ in vitro, indicating a long-lasting Th1 cell phenotype after FMD vaccination. VP3-specific CD4+ T cells exhibited the highest frequency amongst the identified epitopes, comprising >0·004% of the CD4+ T-cell population. CD45RO+CCR7+ defined central memory CD4+ T-cell subpopulations were present in higher frequency in FMDV-specific CD4+ T-cell populations from FMD-vaccinated cattle ex vivo. This indicates an important role in maintaining cell adaptive immunity after FMD vaccination. Notably, FMDV epitope-loaded tetramers detected the presence of FMDV-specific CD4+ T cells in bovine PBMC more than four years after vaccination. This work contributes to our understanding of vaccine efficacy.
DOI： 10.1111/imm.13367
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Lkham-Erdene B., Choijookhuu N., Kubota T., Uto T., Mitoma S., Shirouzu S., Ishizuka T., Kai K., Higuchi K., Aung K.M., Batmunkh J.E., Sato K., Hishikawa Y.
Ａｃｔａ Ｈｉｓｔｏｃｈｅｍｉｃａ ｅｔ Ｃｙｔｏｃｈｅｍｉｃａ 57 ( 5 ) 175 - 188 2024年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本組織細胞化学会
Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a major health problem worldwide. Liver regeneration is crucial for restoring liver function, and is regulated by extraordinary complex process, involving numerous factors under both physiologic and pathologic conditions. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid synthesized by sphingosine kinase 1 (SphK1), plays an important role in liver function through S1P receptors (S1PRs)-expressing cells. In this study, we investigated the effect of lipid overload on hepatocyte proliferation in a mouse hepatic steatosis model induced by feeding a methionine-and choline-deficient (MCD) diet. After 50% partial hepatectomy (PHx), liver tissues were sampled at various timepoints and then analyzed by immunohistochemistry, oil Red-O staining, quantitative-polymerase chain reaction (qPCR), and flow cytometry. In mice fed the MCD-diet, significantly exacerbated hepatic steatosis and accelerated liver regeneration were observed. After PHx, hepatocyte proliferation peaked at 48 and 36 hr in the liver of chow-and MCD-diet fed mice, respectively. By contrast, increased expression of S1PR2 was observed in hepatic neutrophils and macrophages of MCD-diet fed mice. Flow cytome-try and qPCR experiments demonstrated that levels of HGF and FGF2 released by neutrophils and macrophages were significantly higher in MCD-diet fed mice. In conclusion, hepatic lipid overload recruits Kupffer cells and neutrophils that release HGF and FGF2 via SphK1/S1PR2 activation to accelerate hepatocyte proliferation.
DOI： 10.1267/ahc.24-00046
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Tominaga M., Uto T., Fukaya T., Mitoma S., Riethmacher D., Umekita K., Yamashita Y., Sato K.
Frontiers in Immunology 15 1200461 - 1200461 2024年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Frontiers in Immunology
Dendritic cells (DCs) are known as unique professional antigen (Ag)-presenting cells (APCs) to prime naïve T cells for the initiation of adaptive immunity. While DCs are believed to play a pivotal role in generating anti-tumor T-cell responses, the importance of DCs in the protection from the progression of tumors remains elusive. Here, we show how the constitutive deficiency of CD11chi DCs influences the progression of tumors with the use of binary transgenic mice with constitutive loss of CD11chi DCs. Constitutive loss of CD11chi DCs not only enhances the progression of tumors but also reduces the responses of Ag-specific T cells. Furthermore, the congenital deficiency of CD11chi DCs generates the immunosuppressive tumor microenvironment (TME) that correlates with the marked accumulation of myeloid-derived suppressor cells (MDSCs) and the prominent productions of immunosuppressive mediators. Thus, our findings suggest that CD11chi DCs are crucial for generating anti-tumor T-cell responses and immunogenic TME to suppress the development of tumors.
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Yuuka Masuda, Hesham Nasser, Jiri Zahradnik, Shuya Mitoma, Ryo Shimizu, Kayoko Nagata, Akifumi Takaori-Kondo, Gideon Schreiber, Kotaro Shirakawa, Akatsuki Saito, Terumasa Ikeda, Jumpei Ito, Kei Sato
Frontiers in Virology 3 2023年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Frontiers Media SA
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has substantially diversified during the pandemic, resulting in the successive emergence of variants characterized by various mutations. It has been observed that several epidemic variants, including those classified as variants of concern, share mutations at four key residues (L452R, T478K, E484K, and N501Y) within the receptor binding motif (RBM) region of the spike protein. However, the processes through which these four specific RBM mutations were acquired during the evolution of SARS-CoV-2, as well as the degree to which they enhance viral fitness, remain unclear. Moreover, the effect of these mutations on the properties of the spike protein is not yet fully understood. In this study, we performed a comprehensive phylogenetic analysis and showed that the four RBM mutations have been convergently acquired across various lineages throughout the evolutionary history of SARS-CoV-2. We also found a specific pattern in the order of acquisition for some of these mutations. Additionally, our epidemic dynamic modeling demonstrated that acquiring these mutations leads to an increase in the effective reproduction number of the virus. Furthermore, we engineered mutant spike proteins with all feasible combinations of the four mutations, and examined their properties to uncover the influence that these mutations have on viral characteristics. Our results provide insights into the roles these four mutations play in shaping the viral characteristics, epidemic proliferation, and evolutionary pathway of SARS-CoV-2.
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Multiple mutations of SARS-CoV-2 Omicron BA.2 variant orchestrate its virological characteristics 査読あり
Kimura I., Yamasoba D., Nasser H., Ito H., Zahradnik J., Wu J., Fujita S., Uriu K., Sasaki J., Tamura T., Suzuki R., Deguchi S., Plianchaisuk A., Yoshimatsu K., Kazuma Y., Mitoma S., Schreiber G., Asakura H., Nagashima M., Sadamasu K., Yoshimura K., Takaori-Kondo A., Ito J., Shirakawa K., Takayama K., Irie T., Hashiguchi T., Nakagawa S., Fukuhara T., Saito A., Ikeda T., Sato K.
Journal of Virology 97 ( 10 ) 2023年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Virology
Previous studies on the Omicron BA.2 variant suggested that the virological characteristics of BA.2 are determined by the mutations in at least two different regions of the viral genome: in the BA.2 spike gene (enhancing viral fusogenicity and intrinsic pathogenicity) and the non-spike region of the BA.2 genome (leading to intrinsic pathogenicity attenuation). However, the mutations modulating the BA.2 virological properties remain elusive. In this study, we demonstrated that the L371F substitution in the BA.2 spike protein confers greater fusogenicity and intrinsic pathogenicity. Furthermore, we revealed that multiple mutations downstream of the spike gene in the BA.2 genome are responsible for attenuating intrinsic viral pathogenicity and replication capacity. As mutations in the SARS-CoV-2 variant spike proteins could modulate certain virological properties, such as immune evasion and infectivity, most studies have previously focused on spike protein mutations. Our results underpin the importance of non-spike protein-related mutations in SARS-CoV-2 variants. IMPORTANCE Most studies investigating the characteristics of emerging SARS-CoV-2 variants have been focusing on mutations in the spike proteins that affect viral infectivity, fusogenicity, and pathogenicity. However, few studies have addressed how naturally occurring mutations in the non-spike regions of the SARS-CoV-2 genome impact virological properties. In this study, we proved that multiple SARS-CoV-2 Omicron BA.2 mutations, one in the spike protein and another downstream of the spike gene, orchestrally characterize this variant, shedding light on the importance of Omicron BA.2 mutations out of the spike protein.
DOI： 10.1128/jvi.01011-23
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宮崎県における牛ウイルス性下痢の積極的疫学調査と分離株の遺伝子系統解析
野津 昂亮, 龍 千香, Ul Hakim Bin Rahmat Luqman, Ullah Shakir, 植木 萌葉, 三苫 修也, 乗峰 潤三, 青木 博史, 亀山 健一郎, 迫田 義博, 関口 敏
獣医疫学雑誌 28 ( 1 ) 20 - 21 2024年7月
記述言語：日本語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：獣医疫学会
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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.
深谷知宏, 宇都倫史, 三苫修也, 佐藤克明
Veterinary Immunology for Practitioners ( 35 ) 2024年
記述言語：日本語 掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）
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牛伝染性リンパ腫の抵抗性判別 招待あり
関口敏, 三苫修也, 野津昴亮
臨床獣医 42 ( 6 ) 2024年
記述言語：日本語 掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）
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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.
深谷知宏, 宇都倫史, 三苫修也, 佐藤克明
Veterinary Immunology for Practitioners ( 34 ) 15 - 21 2024年
記述言語：日本語 掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）
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樹状細胞を標的とした新規免疫チェックポイント阻害剤の開発
宇都倫史, 深谷知宏, 三苫修也, 佐藤克明
化学工業 74 ( 1 ) 19 - 24 2023年5月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）
講演・口頭発表等 【 表示 ／ 非表示 】
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ルシフェラーゼ融合蛋白結合抗体捕捉法を用いた抗牛伝染性リンパ腫ウイルス抗体検出法の開発
内田 大紀, 三苫 修也, 野津 昂亮, 関口 敏
第167回日本獣医学会学術集会 2024年9月10日
開催年月日： 2024年9月10日 - 2024年9月13日
会議種別：口頭発表（一般）
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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年9月10日
開催年月日： 2024年9月10日 - 2024年9月13日
会議種別：口頭発表（一般）
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Selective cell stimulation with bovine interleukin-2 mutein and the distribution of bovine CD122 on the peripheral lymphocytes
Shuya Mitoma, Tomofumi Uto, Tomohiro Fukaya, Moe Tominaga, Katsuaki Sato, Junzo Norimine
第52回日本免疫学会学術集会 2024年1月17日
開催年月日： 2024年1月17日 - 2024年1月19日
記述言語：英語 会議種別：ポスター発表
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外部導入牛における牛白血病ウイルス感染の定量的リスク分析
野津昂亮, WIRATSUDAKUL Anuwat, 三苫修也, 乗峰潤三, 関口敏
日本産業動物獣医学会(九州)・日本小動物獣医学会(九州)・日本獣医公衆衛生学会(九州) 2017年
開催年月日： 2017年
会議種別：口頭発表（一般）
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宮崎県における肉用牛生産者を対象とした牛白血病対策に関する意識調査
森山楓栞, 耕野拓一, 窪田さと子, 三苫修也, 目堅博久, 乗峰潤三, 関口敏
日本産業動物獣医学会(九州)・日本小動物獣医学会(九州)・日本獣医公衆衛生学会(九州) 2017年
開催年月日： 2017年
会議種別：口頭発表（一般）
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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牛伝染性リンパ腫ウイルス感染症に対するNK細胞選択的活性による防御免疫効果
研究課題/領域番号：22K15013 2022年04月 - 2025年03月
日本学術振興会 科学研究費基金 若手研究
三苫 修也
担当区分：研究代表者
寄附金・講座・研究部門 【 表示 ／ 非表示 】
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感染症学講座免疫学分野研究奨学金(ﾆｯﾎﾟﾝﾊﾑ食の未来財団)
寄附者名称：公益財団法人ﾆｯﾎﾟﾝﾊﾑ食の未来財団 2024年02月