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Affiliation |
Faculty of Agriculture Region of Marine Life Science |
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Associate Professor |
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Related SDGs |
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KONO Tomoya
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Research Areas 【 display / non-display 】
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Life Science / Aquatic bioproduction science
Papers 【 display / non-display 】
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Washim M.R., Morimoto N., Sumiyoshi T., Nishihara A., Nallaperumal S., Kono T., Hikima J.i.
Fish and Shellfish Immunology 171 2026.4
Language：English Publishing type：Research paper (scientific journal) Publisher：Fish and Shellfish Immunology
Interleukin-1β is a pro-inflammatory cytokine with pluripotent roles in mediating immune response. In fish, IL-1β plays a major role in inflammatory responses to pathogenic infections, though its immunological functions through direct stimulation have not been studied in detail. In this study, two IL-1β genes (il1b1 and il1b2) from the Japanese medaka (Oryzias latipes) were identified and characterized. The broad immunostimulatory effects of recombinant IL-1β (OlrIL-1β) from Japanese medaka were explored using embryonic fibroblast-like cell line (OLHdrR-e3) and primary cultured kidney cells. Recombinant proteins were produced via prokaryotic expression based on predicted mature isoforms IL-1β1_Asp<sup>95</sup> (type II) and IL-1β2_Asp<sup>121</sup> (type I) to investigate their distinct functional characteristics. Then, their immune-related gene expression, phagocytosis, and reactive oxygen species (ROS) production ability were evaluated in vitro and ex vivo. rIL-1β triggers the expression of not only pro-inflammatory cytokines such as il1b, tnfa, il6, il8, mcp1b, and csf1b, but also the antimicrobial peptide, def1b. Additionally, they upregulate the expression of cell specific markers, including macrophage- and granulocyte-specific genes mpeg1.1, mpx2, and epx, and nitric oxide synthase (NO) gene nos1. Moreover, medaka OlrIL-1β proteins exhibited robust phagocytosis and superoxide anion production ability than those in unstimulated control. In all evaluations, the OlrIL-1β proteins corresponding to the predicted cleavage sites exhibited strong immune activation, with type I OlIL-1β2_Asp<sup>121</sup> demonstrating more potent response than type II. To our knowledge, this is the study to reveal the immunomodulatory functions of Japanese medaka IL-1β, highlighting its potential in immunotherapy for disease prevention and control in aquaculture.
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Nishihara A., Sumiyoshi T., Washim M.R., Yasumoto S., Kondo M., Kono T., Hikima J.i.
Aquaculture 608 2025.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Aquaculture
Edwardsiella piscicida (Enterobacteriaceae) is an important fish pathogen that causes edwardsiellosis in many species, including Japanese flounder (Paralichthys olivaceus), leading to economic losses in aquaculture. We investigated the direct inhibitory activity of IvyEp (Inhibitors of vertebrate lysozyme derived from E. piscicida) against host C-type lysozyme, and its role in host immune evasion. The results of functional assays confirmed that IvyEp significantly inhibited the activity of hen egg white lysozyme (HEWL), and kinetic analysis demonstrated that IvyEp acts as a competitive inhibitor. The ivy-deleted strain of E. piscicida exhibited reduced virulence in Japanese medaka (Oryzias latipes) and flounder infection models, highlighting its role in immune evasion and pathogenicity. IvyEp significantly suppressed lysozyme-like activity in the serum of Japanese flounder, yellowtail (Seriola quinqueradiata), and Nile tilapia (Oreochromis niloticus), suggesting broad-spectrum inhibition of C-type lysozymes across these species. Further assays confirmed that IvyEp significantly inhibited the lytic activity of purified flounder C-type lysozyme (rLyzC), supporting the hypothesis that IvyEp directly interferes with host lysozyme activity. Structural analysis predicted that IvyEp blocks the active site of rLyzC through electrostatic interactions, preventing substrate binding, and thus neutralizing rLyzC function. Co-immunoprecipitation revealed that IvyEp directly binds to HEWL and rLyzC. These findings provide new insights into the potential role of IvyEp in protecting E. piscicida from host immune responses and suggest its probable function as a universal C-type lysozyme inhibitor across different fish species.
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Yamamoto J., Deguchi H., Sumiyoshi T., Nakagami K., Saito A., Miyanishi H., Kondo M., Kono T., Sakai M., Kinoshita M., Hikima J.I.
Marine Biotechnology 26 ( 4 ) 658 - 671 2024.8
Publishing type：Research paper (scientific journal) Publisher：Marine Biotechnology
Intracellular bacteria such as those belonging to the genus Edwardsiella can survive and proliferate within macrophages. However, the detailed mechanisms underlying the host macrophage immune response and pathogen evasion strategies remain unknown. To advance the field of host macrophage research, we successfully established transgenic (Tg) Japanese medaka Oryzias latipes that possesses fluorescently visualized macrophages. As a macrophage marker, the macrophage-expressed gene 1.1 (mpeg1.1) was selected because of its predominant expression across various tissues in medaka. To validate the macrophage characteristics of the fluorescently labeled cells, May-Grünwald Giemsa staining and peroxidase staining were conducted. The labeled cells exhibited morphological features consistent with those of monocyte/macrophage-like cells and tested negative for peroxidase activity. Through co-localization studies, the fluorescently labeled cells co-localized with E. piscicida in the intestines and kidneys of infected medaka larvae, confirming the ingestion of bacteria through phagocytosis. In addition, the labeled cells expressed macrophage markers but lacked a neutrophil marker. These results suggested that the fluorescently labeled cells of Tg[mpeg1.1:mCherry/mAG] medaka were monocytes/macrophages, which will be useful for future studies aimed at understanding the mechanisms of macrophage-mediated bacterial infections.
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Accumulation and Phagocytosis of Fluorescently Visualized Macrophages Against Edwardsiella piscicida Infection in Established mpeg1.1‑Transgenic Japanese Medaka Oryzias latipes Reviewed
Juna Yamamoto, Hana Deguchi, Takechiyo Sumiyoshi, Kentaro Nakagami, Akatsuki Saito, Hiroshi Miyanishi, Masakazu Kondo, Tomoya Kono, Masahiro Sakai1, Masato Kinoshita, Jun‑ichi Hikima
Marine Biotechnology 26 658 - 671 2024.6
Language：English Publishing type：Research paper (scientific journal)
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Comprehensive analysis of diel rhythmic expression of the medaka tlr gene family Reviewed
Takahiko Hata, Suzuka Setoguchi, Natuki Morimoto, Hidetoshi Shimawaki, Jun-ichi Hikima, Masahiro Sakai, Tomoya Kono
Developmental and Comparative Immunology in press 2024.5
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)
Books 【 display / non-display 】
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月刊「養殖」サイトカインを用いた魚類免疫賦活剤の効果判定
酒井正博・高山博章・河野智哉（ Role： Joint author）
緑書房 2012.2
Responsible for pages：54-57 Language：Japanese
MISC 【 display / non-display 】
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Nishihara Aki, Sumiyoshi Takechiyo, Arakawa Koushiro, Morimoto Natsuki, Yasumoto Shinya, Kondo Masakazu, Kono Tomoya, Sakai Masahiro, Hikima Jun-ichi
Fish Pathology 58 ( 4 ) 175 - 179 2023
Language：English Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：The Japanese Society of Fish Pathology
<i>Edwardsiella</i> bacteria infect Japanese medaka <i>Oryzias latipes</i>; however, the difference in susceptibility between <i>E. piscicida</i> and <i>E. anguillarum</i> is unknown. In this study, we performed challenge tests with medaka using four <i>Edwardsiella</i> strains, which were difficult to be identified by specific primers. The four strains were reclassified as three <i>E. piscicida</i> strains and one <i>E. anguillarum</i> strain using phylogenetic analysis. The immersion challenge demonstrated that medaka were more susceptible to <i>E. piscicida</i> than to <i>E. anguillarum</i>. Increases in the bacterial copy number in the infected medaka kidneys were correlated with the worsening of the external symptoms. Medaka is considered a valuable model organism for understanding the etiology of edwardsiellosis.
DOI： 10.3147/JSFP.58.175
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サイトカイン遺伝子を用いた魚類免疫賦活剤の効果判定
酒井正博、高山博章、河野智哉
養殖 2012.2
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media) Publisher：緑書房
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Genomics of fish IL-17 ligand and receptors: A review.
T. Kono, H. Korenaga and M. Sakai
Fish and Shellfish Immunology ( 31 ) 635 - 643 2010.12
Language：English Publishing type：Article, review, commentary, editorial, etc. (scientific journal) Publisher：Elsevier
Presentations 【 display / non-display 】
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銅合金属製生簀網の防汚・抗菌性能に関する調査
荒川孝志朗、澤田梨久、中島智優、室谷冬香、宮村和良、西山雅人、福田穣、阿川泰夫、白樫正、河野智哉、引間順一
令和8年度日本魚病学会春季大会
Event date： 2026.3.7 - 2026.3.8
Presentation type：Poster presentation
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Circadian regulation of Fish Immunology 魚類における免疫リズムの制御
羽田崇彦、平吉美優、引間順一、河野智哉
第32回日本時間生物学会学術大会
Event date： 2025.10.4 - 2025.10.5
Presentation type：Poster presentation
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Edwardsiella piscicida由来TIR結合因子TcpLの機能解明
入鹿誓良、住吉竹千代、近藤昌和、安本信哉、河野智哉、引間順一
令和7年度日本魚病学会秋季大会
Event date： 2025.9.11 - 2025.9.12
Presentation type：Oral presentation (general)
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Immune response of two interleukin-1 isoforms in Japanese medaka
Mizuanur Rahman Washim, Natsuki Morimoto, Takechiyo Sumiyoshi, Tomoya Kono, Jun-ichi Hikima
日本比較免疫学会第36回学術集会
Event date： 2025.8.29 - 2025.8.31
Language：English Presentation type：Oral presentation (general)
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Edwardsiella piscicida由来リゾチーム阻害因子Ivyの機能モチーフ解析およびメダカに対する病原性評価
西原輝、住吉竹千代、安本信哉、近藤昌和、河野智哉、引間順一
日本比較免疫学会第36回学術集会
Event date： 2025.8.29 - 2025.8.31
Language：Japanese Presentation type：Oral presentation (general)
Awards 【 display / non-display 】
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農学特別賞 (研究部門)
2025.2 宮崎大学農学部
羽田崇彦、河野智哉
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2022年 宮崎大学学生農学特別賞表
2023.2 宮崎大学農学部 Diel rhythm of the inflammatory cytokine il1b in the Japanese medaka (Oryzias latipes) regulated by core components of the circadian clock
Tomoya Takeuchi, Takahiko Hata, Hiroshi Miyanishi, Takumi Yuasa, Suzuka Setoguchi, Ayaka Takeda, Natsuki Morimoto, Jun-ichi Hikima, Masahiro Sakai and Tomoya Kono
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日本水産学会 水産学進歩賞
2021.3 日本水産学会 魚類サイトカインによる自然免疫応答の概日リズム制御に関する研究
河野智哉
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
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宮崎大学農学部論文表彰
2018.1 宮崎大学農学部 Identification and immunoregulatory function of neuromedin U (Nmu) in the Japanese pufferfish Takifugu rubripes
河野智哉
Country：Japan
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北里大学同窓会研究奨励賞
2012.9 北里大学 魚類生理活性ペプチドのクロストークによる免疫制御機構の解析
河野智哉
Grant-in-Aid for Scientific Research 【 display / non-display 】
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時刻を考慮した魚病防除技術の開発
Grant number：25KJ1984 2025.04 - 2028.03
独立行政法人日本学術振興会 科学研究費基金 特別研究員奨励費
Authorship：Principal investigator
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魚類と病原体が織りなす感染の概日リズムの究明 ～感染症の防除を目指して～
Grant number：24K01837 2024.04 - 2028.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(B)
Authorship：Principal investigator
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生物時計が調節する魚類の免疫リズムの解明 ～感染症の防除を目指して～
Grant number：20H03064 2020.04 - 2024.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(B)
Authorship：Principal investigator
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フグはなぜ疾病に強いのか？フグの耐病性のメカニズムを探る
Grant number：17H01486 2017.04 - 2021.03
科学研究費補助金 基盤研究(A)
Authorship：Coinvestigator(s)
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魚類の免疫応答における概日リズムの解明～免疫増強剤の効果向上を目指して～
Grant number：17K07915 2017.04 - 2020.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
Available Technology 【 display / non-display 】
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魚類の免疫リズムの解明
魚病の防除を目的とした時間治療法の確立Home Page： 免疫生物学研究室
Related fields where technical consultation is available：・魚類免疫賦活剤の評価
・魚類の健康診断Message：・共同研究の希望テーマ：魚類の免疫力向上に関する研究