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市川　世識 (イチカワ　ヨシキ)

獣医学研究院特任助教

日本獣医病理学専門家協会会員（2025年8月）

研究者基本情報

■ 学位
  • 学士 （獣医学）, 北海道大学, 2020年03月
  • 博士（獣医学）, 北海道大学, 2024年09月
■ URL
researchmap URLホームページURL■ ID 各種
研究者番号
  • 21022550
J-Global ID■ 研究キーワード・分野
研究キーワード
  • 獣医病理学
  • 法獣医学
  • 鼻疽
  • 動物由来感染症
研究分野
  • ライフサイエンス, 獣医学, 獣医病理学
  • ライフサイエンス, 獣医学, 細菌学
■ 担当教育組織

経歴

■ 経歴
経歴
  • 2025年04月 - 現在
    北海道大学 獣医学研究院, 法獣医学分野, 特任助教, 日本国
  • 2021年04月 - 2024年03月
    日本学術振興会, 特別研究員 DC1
学歴
  • 2020年04月 - 2024年03月, 北海道大学, 大学院獣医学院
  • 2014年04月 - 2020年03月, 北海道大学, 獣医学部, 共同獣医学過程

研究活動情報

■ 論文
  • Development of lateral flow assays for the rapid diagnosis of glanders in equids.
    Ryo Shimbo; Kazuki Mizuta; Yoshiki Ichikawa; Enkhtuul Batchuluun; Ochirbat Khurtsbaatar; Ai Koshikawa; Yuta Kinoshita; Hidekazu Niwa; Tomohiro Okagawa; Keisuke Aoshima; Vanaabaatar Batbaatar; Kazuhiko Ohashi; Takashi Kimura
    Microbiology spectrum, e0015426, 2026年07月10日, ［国際誌］
    英語, 研究論文（学術雑誌）, UNLABELLED: Glanders is a contagious zoonotic disease caused by Burkholderia mallei that primarily affects horses, donkeys, and mules. It remains endemic in parts of Asia, Africa, the Middle East, and South America, where increasing case reports highlight the need for accessible diagnostic tools. Conventional diagnostic methods are limited by high costs and specialized laboratory requirements, whereas lateral flow assays (LFAs) offer practical, user-friendly, and rapid alternatives. In this study, we developed three LFAs targeting antibodies against the B. mallei antigens Hcp1, GroEL, and whole-cell lysate (WCL), previously identified as promising markers in indirect enzyme-linked immunosorbent assays. Recombinant streptococcal protein G served as the colloidal gold conjugate. Diagnostic performance was evaluated using glanders-positive (n = 31) and glanders-negative (n = 51) equine sera collected in Mongolia. Hcp1-LFA demonstrated 100% sensitivity and 100% specificity, while WCL-LFA achieved 100% sensitivity and 98.0% specificity. GroEL-LFA showed 100% sensitivity but lower specificity (90.2%). Hcp1- and WCL-LFA also exhibited high sensitivity in asymptomatic horses. No cross-reactivity was observed with sera from horses with other infections (n = 60) collected in Japan. All LFAs remained functional for at least 16 weeks at 37°C. These results indicate that Hcp1- and WCL-based LFAs provide accurate, rapid, and equipment-free detection of glanders. Their simplicity, stability, and affordability make them highly suitable for field diagnosis, especially in low-resource endemic settings. Nonetheless, further validation using larger and more diverse sample sets is required to confirm their broader applicability. IMPORTANCE: Glanders is a contagious disease affecting horses, donkeys, and mules that can have serious economic and animal health consequences. Current diagnostic tests are expensive, time-consuming, and require specialized equipment. The assays developed in this study are simple, rapid, and cost-effective, allowing veterinarians to quickly identify infected animals in the field. Early detection helps prevent the spread of the disease, safeguarding livestock, supporting animal health, and reducing economic losses in affected regions.
  • Development of a Novel Real-Time PCR Assay Differentiating Burkholderia mallei From Burkholderia pseudomallei.
    Ai Koshikawa; Yoshiki Ichikawa; Mitsuru Nakase; Apichai Tuanyok; Vannarat Saechan; Keisuke Aoshima; Hideaki Higashi; Chie Nakajima; Yasuhiko Suzuki; Vanaabaatar Batbaatar; Takashi Kimura
    Microbiology and immunology, 2026年04月29日, ［国際誌］
    英語, 研究論文（学術雑誌）, Glanders is a zoonotic disease caused by Burkholderia mallei (Bm). Bm is phylogenetically similar to B. pseudomallei (Bp), the causative agent of melioidosis, making it difficult to differentiate between them. Recently, the PCR method recommended by the World Organisation for Animal Health (WOAH) failed to detect a Kuwait strain of Bm, and the WOAH has cautioned that ongoing Bm evolution may lead to the emergence of variants that escape standard assays. Therefore, this study aimed to develop a novel real-time PCR method to discriminate between Bm and Bp. Local and web-based BLAST searches identified a 494-bp sequence conserved across Bm but absent from other bacterial genomes, including Bp, except for one B. thailandensis strain. The optimized probe-based real-time PCR targeting this sequence detected the genomes of five Bm isolates but did not amplify DNA from closely related Burkholderia species. In clinical specimens from Mongolia, this assay amplified Bm DNA at an equivalent detection rate to the WOAH-recommended real-time PCR method. These findings provide a novel, highly sensitive diagnostic method for differentiating glanders from melioidosis and suggest its potential use as an alternative method in clinical applications. Further verification using a large number of samples collected from various regions will be necessary in the future.
  • Comparison of immunogenicity of 17 Burkholderia mallei antigens and whole cell lysate using indirect ELISA.
    Yoshiki Ichikawa; Yukiko Iinuma; Tomohiro Okagawa; Ryo Shimbo; Batchuluun Enkhtuul; Ochirbat Khurtsbaatar; Yuta Kinoshita; Hidekazu Niwa; Keisuke Aoshima; Atsushi Kobayashi; Vanaabaatar Batbaatar; Kazuhiko Ohashi; Takashi Kimura
    The Journal of veterinary medical science, 87, 4, 394, 401, 2025年04月01日, ［国内誌］
    英語, 研究論文（学術雑誌）, Glanders is a World Organization for Animal Health (WOAH)-notifiable equine disease caused by the infection of Burkholderia mallei, and is endemic in Mongolia, South Asia, Africa, and South America. While the complement fixation test (CFT) has been widely used for serodiagnosis of glanders and is considered a standard serological test, it has several limitations. These limitations include poor specificity, labor intensive techniques, variability in antigen and protocol. Consequently, indirect enzyme-linked immunosorbent assays (iELISAs) based on recombinant proteins have been developed as alternative serodiagnostic assays to address some of the challenges associated with the CFT. The accuracy of iELISA relies on the B. mallei proteins used as an antigen. Hence, to determine the best diagnostic candidate in iELISA, in terms of sensitivity and specificity, a comparison of 17 immunogenic B. mallei proteins and detergent-based whole cell lysate (WCL) was performed. According to the sensitivity and specificity on the sera from glanderous and non-glanderous Mongolian native horses, iELISA using Hcp1, GroEL, and detergent-based WCL represented the highest diagnostic accuracy. These three candidates did not have cross-reactivity to horse sera with several other equine diseases. WCL, Hcp1, and GroEL showed considerable potential as antigens for iELISA in the serodiagnosis of glanders in Mongolia. Detergent-based WCL extraction offers a consistent approach for the preparation of reliable B. mallei antigen. WCL-iELISA should be further validated in a large-scale study to meet WOAH demands.
  • First molecular characterization of Burkholderia mallei strains isolated from horses in Mongolia
    Yoshiki Ichikawa; Liushiqi Borjigin; Batchuluun Enkhtuul; Ochirbat Khurtsbaatar; Keisuke Aoshima; Atsushi Kobayashi; Vanaabaatar Batbaatar; Takashi Kimura
    Infection, Genetics and Evolution, 123, 105616, 105616, Elsevier BV, 2024年09月
    研究論文（学術雑誌）
  • Systemic mucoid degeneration of the arterial tunica intima in a young dog
    Yoshiki Ichikawa; Mizuki Heishima; Kristin Vyhnal; Keisuke Aoshima; Kazuyoshi Sasaoka; Ryohei Kinoshita; Atsushi Kobayashi; Mitsuyoshi Takiguchi; Takashi Kimura
    Journal of Veterinary Diagnostic Investigation, 34, 1, 94, 97, SAGE Publications, 2021年09月04日
    研究論文（学術雑誌）, A 27-mo-old, spayed female mixed-breed dog was presented with left forelimb pain, which progressed to full thickness necrosis of the soft tissues of multiple limbs. Clinical imaging and postmortem examination suggested multiple large arterial thromboemboli. Histologic examination of vascular lesions revealed markedly thickened tunica intima with polypoid intraluminal projections, which partially to entirely occluded the arterial lumen. The expanded tunica intima was comprised of intimal accumulation of Alcian blue–positive matrix with scattered spindle-to-satellite cells. These cells were positive for von Willebrand factor and vimentin but negative for α–smooth muscle actin, suggesting endothelial origin. Deposition of the intimal mucoid matrix was observed in the elastic and muscular arteries associated with regional ischemic changes. Mucoid emboli, likely from fragmentation of proliferative intimal tissue, were identified in smaller vessels supplied by affected arteries. Based on these findings, we diagnosed systemic mucoid degeneration of the arterial tunica intima. Such systemic arterial degeneration characterized by deposition of mucoid matrix in the tunica intima has not been reported previously in dogs, to our knowledge, and should be distinguished from thromboembolism and other degenerative vascular diseases.
  • Programmed death‐ligand 1 expression in swine chronic infections and enhancement of interleukin‐2 production via programmed death‐1/programmed death‐ligand 1 blockade
    Otgontuya Ganbaatar; Satoru Konnai; Tomohiro Okagawa; Yutaro Nojima; Naoya Maekawa; Yoshiki Ichikawa; Atsushi Kobayashi; Tomoyuki Shibahara; Yojiro Yanagawa; Hidetoshi Higuchi; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
    Immunity, Inflammation and Disease, 9, 4, 1573, 1583, Wiley, 2021年08月20日
    研究論文（学術雑誌）, Abstract

    Introduction

    Chronic infections lead to the functional exhaustion of T cells. Exhausted T cells are phenotypically differentiated by the surface expression of the immunoinhibitory receptor, such as programmed death‐1 (PD‐1). The inhibitory signal is produced by the interaction between PD‐1 and its PD‐ligand 1 (PD‐L1) and impairs the effector functions of T cells. However, the expression dynamics of PD‐L1 and the immunological functions of the PD‐1/PD‐L1 pathway in chronic diseases of pigs are still poorly understood. In this study, we first analyzed the expression of PD‐L1 in various chronic infections in pigs, and then evaluated the immune activation by the blocking assay targeting the swine PD‐1/PD‐L1 pathway.

    Methods

    In the initial experiments, anti‐bovine PD‐L1 monoclonal antibodies (mAbs) were tested for cross‐reactivity with swine PD‐L1. Subsequently, immunohistochemical analysis was conducted using the anti‐PD‐L1 mAb. Finally, we assessed the immune activation of swine peripheral blood mononuclear cells (PBMCs) by the blockade with anti‐PD‐L1 mAb.

    Results

    Several anti‐PD‐L1 mAbs tested recognized swine PD‐L1‐expressing cells. The binding of swine PD‐L1 protein to swine PD‐1 was inhibited by some of these cross‐reactive mAbs. In addition, immunohistochemical analysis revealed that PD‐L1 was expressed at the site of infection in chronic infections of pigs. The PD‐L1 blockade increased the production of interleukin‐2 from swine PBMCs.

    Conclusions

    These findings suggest that the PD‐1/PD‐L1 pathway could be also involved in immunosuppression in chronic infections in pigs. This study provides a new perspective on therapeutic strategies for chronic diseases in pigs by targeting immunosuppressive pathways.
  • Expression Analysis of Canine CMTM6 and CMTM4 as Potential Regulators of the PD-L1 Protein in Canine Cancers
    Hiroto Takeuchi; Satoru Konnai; Naoya Maekawa; Erina Minato; Yoshiki Ichikawa; Atsushi Kobayashi; Tomohiro Okagawa; Shiro Murata; Kazuhiko Ohashi
    Frontiers in Veterinary Science, 7, Frontiers Media SA, 2020年06月11日
    研究論文（学術雑誌）
■ その他活動・業績
■ 共同研究・競争的資金等の研究課題
  • ふれあい展示されるエキゾチックアニマルの微生物学的リスク管理に資する研究
    科学研究費助成事業
    2026年04月01日 - 2029年03月31日
    市川 世識
    日本学術振興会, 若手研究, 北海道大学, 26K18187
  • 細胞内寄生菌に対する新規治療法を目指した パイロトーシス誘導メカニズムの解明
    科学研究費助成事業
    2023年03月08日 - 2024年03月31日
    市川 世識
    細胞株を用いたパイロトーシス制御経路の解析については、東北大学加齢医学研究所附属医用細胞資源センターより分譲していただいたTHP-1細胞を用いた。THP-1細胞はマウス単球由来の細胞株であり、フォルボールエステルにてマクロファージに分化させることができる。 RAW264.1細胞やJ774細胞と異なり、THP-1細胞はパイロトーシスに関連するタンパク質を正常に発現することが分かっている。THP-1細胞をフォルボールエステルでマクロファージに分化させる過程で、すでにCOX-2を発現することが分かったため、COX阻害薬であるインドメタシンを培地に加えて２時間処理すると、Arginase-2の遺伝子発現量が2.4倍増加することが分かった。Arginase-2は以前の実験においてパイロトーシスの誘導に関与すると示唆された遺伝子である。
    細胞内寄生菌感染動物の病理組織学的解析については、本年度はパイロトーシスに関わるタンパク質としてcleaved caspase-1, Arginase-2の発現局在を解析した。cleaved casepase-1はGasderminを活性型に変換する酵素であり、活性型Gasderminは細胞膜に孔を開け、パイロトーシスを引き起こす。解析に使用した病理切片は、本研究室に保存されている細胞内寄生菌感染動物のホルマリン固定パラフィン包埋切片を用いた。ロドコッカスエクイ感染仔馬の肺・回腸において、膿瘍を形成する好中球はArginase-2に弱陽性を示し、cleaved caspase-1の発現は認められなかった。また、ヨーネ病感染牛の回腸では、ヨーネ菌に感染している類上皮細胞などの炎症性細胞にcleaved caspase-1, Arginase-2の発現は認められなかった。
    日本学術振興会, 特別研究員奨励費, 北海道大学, 22KJ0028