高橋 大輔 (タカハシ ダイスケ)

Takahashi, Daisuke

写真a

所属(所属キャンパス)

薬学部 薬科学科 生化学講座 (芝共立)

職名

専任講師

外部リンク

経歴 【 表示 / 非表示

  • 2008年04月
    -
    2012年03月

    RIKEN RCAI

  • 2012年04月
    -
    2015年03月

    La Jolla Institute for Allergy & Immunology

学位 【 表示 / 非表示

  • Ph.D., 横浜市立大学, 課程, 2011年11月

 

研究分野 【 表示 / 非表示

  • ライフサイエンス / 細胞生物学 (腸上皮細胞)

  • ライフサイエンス / 免疫学 (T細胞)

研究キーワード 【 表示 / 非表示

  • 制御性T細胞

  • 粘膜免疫学

  • 腸上皮細胞

  • 腸上皮細胞間リンパ球

  • 酪酸

研究テーマ 【 表示 / 非表示

  • 腸管上皮細胞と上皮間リンパ球の相互作用の解析, 

    2015年04月
    -
    継続中

  • 腸内細菌が産生する短鎖脂肪酸が関節リウマチを抑制するメカニズムの解明, 

    2015年04月
    -
    継続中

 

論文 【 表示 / 非表示

  • AP-1B regulates interactions of epithelial cells and intraepithelial lymphocytes in the intestine.

    Matsumoto R, Ogata K, Takahashi D, Kinashi Y, Yamada T, Morita R, Tanaka K, Hattori K, Endo M, Fujimura Y, Sasaki N, Ohno H, Ishihama Y, Kimura S, Hase K

    Cellular and molecular life sciences : CMLS (Springer Science and Business Media LLC)  81 ( 1 ) 425 2024年10月

    査読有り,  ISSN  1420-682X

  • Intestinal epithelium dysfunctions cause IgA deposition in the kidney glomeruli of intestine-specific Ap1m2-deficient mice.

    Kinashi Y, Tanaka K, Kimura S, Hirota M, Komiyama S, Shindo T, Hashiguchi A, Takahashi D, Shibata S, Karaki SI, Ohno H, Hase K

    EBioMedicine 106   105256 - 105256 2024年07月

    査読有り,  ISSN  2352-3964

     概要を見る

    Background: Intestinal epithelial cells (IECs) serve as robust barriers against potentially hostile luminal antigens and commensal microbiota. Epithelial barrier dysfunction enhances intestinal permeability, leading to leaky gut syndrome (LGS) associated with autoimmune and chronic inflammatory disorders. However, a causal relationship between LGS and systemic disorders remains unclear. Ap1m2 encodes clathrin adaptor protein complex 1 subunit mu 2, which facilitates polarized protein trafficking toward the basolateral membrane and contributes to the establishment of epithelial barrier functions. Methods: We generated IEC-specific Ap1m2-deficient (Ap1m2ΔIEC) mice with low intestinal barrier integrity as an LSG model and examined the systemic impact. Findings: Ap1m2ΔIEC mice spontaneously developed IgA nephropathy (IgAN)-like features characterized by the deposition of IgA–IgG immune complexes and complement factors in the kidney glomeruli. Ap1m2 deficiency markedly enhanced aberrantly glycosylated IgA in the serum owing to downregulation and mis-sorting of polymeric immunoglobulin receptors in IECs. Furthermore, Ap1m2 deficiency caused intestinal dysbiosis by attenuating IL-22-STAT3 signaling. Intestinal dysbiosis contributed to the pathogenesis of IgAN because antibiotic treatment reduced aberrantly glycosylated IgA production and renal IgA deposition in Ap1m2ΔIEC mice. Interpretation: IEC barrier dysfunction and subsequent dysbiosis by AP-1B deficiency provoke IgA deposition in the mouse kidney. Our findings provide experimental evidence of a pathological link between LGS and IgAN. Funding: AMED, AMED-CREST, JSPS Grants-in-Aid for Scientific Research, JST CREST, Fuji Foundation for Protein Research, and Keio University Program for the Advancement of Next Generation Research Projects.

  • Sugar and arginine facilitate oral tolerance by ensuring the functionality of tolerogenic immune cell subsets in the intestine.

    Nagai M, Okawa T, Nakata K, Takahashi D, Miyajima R, Shiratori H, Yamanaka D, Nakamura A, Oyama C, Takahashi SI, Toyama-Sorimachi N, Suzuki K, Ohashi W, Dohi T, Kawamura YI, Hase K

    Cell reports (Elsevier BV)  43 ( 7 ) 114490 - 114490 2024年07月

    査読有り,  ISSN  2211-1247

     概要を見る

    Although oral tolerance is a critical system in regulating allergic disorders, the mechanisms by which dietary factors regulate the induction and maintenance of oral tolerance remain unclear. To address this, we explored the differentiation and function of various immune cells in the intestinal immune system under fasting and ad libitum-fed conditions before oral ovalbumin (OVA) administration. Fasting mitigated OVA-specific Treg expansion, which is essential for oral tolerance induction. This abnormality mainly resulted from functional defects in the CX3CR1+ cells responsible for the uptake of luminal OVA and reduction of tolerogenic CD103+ dendritic cells. Eventually, fasting impaired the preventive effect of oral OVA administration on asthma and allergic rhinitis development. Specific food ingredients, namely carbohydrates and arginine, were indispensable for oral tolerance induction by activating glycolysis and mTOR signaling. Overall, prior food intake and nutritional signals are critical for maintaining immune homeostasis by inducing tolerance to ingested food antigens.

  • A purified diet affects intestinal epithelial proliferation and barrier functions through gut microbial alterations.

    Shiratori H, Hattori KM, Nakata K, Okawa T, Komiyama S, Kinashi Y, Kabumoto Y, Kaneko Y, Nagai M, Shindo T, Moritoki N, Kawamura YI, Dohi T, Takahashi D, Kimura S, Hase K

    International immunology (Oxford University Press (OUP))  36 ( 5 ) 223 - 240 2024年01月

    査読有り,  ISSN  0953-8178

     概要を見る

    The gut microbiota plays a crucial role in maintaining epithelial barrier function. Although multiple studies have demonstrated the significance of dietary factors on gut microbiota and mucosal barrier function, the impact of a purified diet, which has long been used in various animal experiments, on intestinal homeostasis remains to be elucidated. Here, we compared the impact of two different types of diets, a crude diet and an AIN-93G-formula purified diet, on epithelial integrity and the gut microbiota. Purified diet-fed mice exhibited shorter villi and crypt lengths and slower epithelial turnover, particularly in the ileum. In addition, antimicrobial products, including islet-derived protein 3γ (REG3γ), were substantially decreased in purified diet-fed mice. Purified diet feeding also suppressed α1,2-fucosylation on the epithelial surface. Furthermore, purified diet induced metabolic rewiring to fatty acid oxidation and ketogenesis. 16S ribosomal RNA gene sequencing of the ileal contents and mucus layer revealed distinct gut microbiota compositions between the purified and crude diet-fed mice. Purified diet feeding reduced the abundance of segmented filamentous bacteria (SFB), which potently upregulate REG3γ and fucosyltransferase 2 (Fut2) by stimulating group 3 innate lymphoid cells (ILC3) to produce IL-22. These observations illustrate that the intake of a crude diet secures epithelial barrier function by facilitating SFB colonization, whereas a purified diet insufficiently establishes the epithelial barrier, at least partly owing to the loss of SFB. Our data suggest that the influence of purified diets on the epithelial barrier integrity should be considered in experiments using purified diets.

  • Safe and efficient oral allergy immunotherapy using one-pot-prepared mannan-coated allergen nanoparticles.

    Li S, Toriumi H, Takahashi D, Kamasaki T, Fujioka Y, Nagatoishi S, Li J, Liu Y, Hosokawa T, Tsumoto K, Ohba Y, Katayama Y, Murakami D, Hase K, Mori T

    Biomaterials (Elsevier BV)  303   122381 - 122381 2023年12月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  0142-9612

     概要を見る

    Allergen immunotherapy (AIT) is the only curative treatment for allergic diseases. However, AIT has many disadvantages related to efficiency, safety, long-term duration, and patient compliance. Dendritic cells (DCs) have an important role in antigen-specific tolerance induction; thus, DC-targeting strategies to treat allergies such as glutaraldehyde crosslinked antigen to mannoprotein (MAN) have been established. However, glutaraldehyde crosslinking may reduce the antigen presentation efficiency of DCs. To overcome this, we developed a MAN-coated ovalbumin (OVA) nanoparticle (MDO), which uses intermolecular disulfide bond to crosslink OVA and MAN. MDO effectively targeted DCs resulting in tolerogenic DCs, and promoted higher antigen presentation efficiency by DCs compared with OVA or glutaraldehyde crosslinked nanoparticles. In vitro and in vivo experiments showed that DCs exposed to MDO induced Treg cells. Moreover, MDO had low reactivity with anti-OVA antibodies and did not induce anaphylaxis in allergic mice, demonstrating its high safety profile. In a mouse model of allergic asthma, MDO had significant preventative and therapeutic effects when administered orally or subcutaneously. Therefore, MDO represents a promising new approach for the efficient and safe treatment of allergies.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

総説・解説等 【 表示 / 非表示

  • The Roles of Peyer's Patches and Microfold Cells in the Gut Immune System: Relevance to Autoimmune Diseases

    Nobuhide Kobayashi*, Daisuke Takahashi* (*equal contribution), Shunsuke Takano, Shunsuke Kimura and Koji Hase

    frontiers in Immunology (Frontiers Media S.A.)   2019年12月

    記事・総説・解説・論説等(学術雑誌)

  • 自己免疫疾患の発症を制御する短鎖脂肪酸

    長谷 耕二、髙橋 大輔

    腸内細菌-宿主のクロストークと食事要因 (建帛社)     191 - 200 2019年05月

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア), 共著

  • 腸管免疫学研究のフロントライン

    松本 龍太郎, 髙橋 大輔, 長谷 耕二

    免疫・炎症病態×治療 Update (南山堂)     192 - 199 2019年05月

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)

  • 腸内細菌と自己免疫疾患

    髙橋 大輔、長谷 耕二

    実験医学増刊 腸内細菌叢 健康と疾患を制御するエコシステム 137   91 - 96 2019年02月

    共著

  • 短鎖脂肪酸による免疫・代謝制御

    髙橋 大輔長谷 耕二

    血管医学 17 2016年10月

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア), 共著

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研究発表 【 表示 / 非表示

  • Microbial fermentation product butyrate Ameliorates Autoimmune Arthritis.

    Daisuke Takahashi, Trevor Lockett, Julie M Clarke, David L Topping, Koji Hase

    The 46th Annual Meeting of The Japanese Society for Immunology, 

    2017年12月

    口頭発表(一般)

  • 腸内細菌代謝物の酪酸によるIgA産生細胞誘導機構の解明

    髙橋 大輔長谷 耕二

    第46回日本腎臓学会西部学術大会, 

    2016年10月

    口頭発表(招待・特別)

  • The microbial metabolite butyrate attenuates autoimmune arthritis in mice.

    Daisuke Takahashi, Koji Hase

    フォーラム2016 衛生薬学・環境トキシコロジー, 

    2016年09月

    口頭発表(招待・特別)

  • Microbial fermentation product butyrate Ameliorates Autoimmune Arthritis.

    Takahashi Daisuke

    International Congress of Immunology 2016 (ICI2016) (Australia Melbourne) , 

    2016年08月

    ポスター発表

  • 「腸内細菌由来の酪酸を介した免疫システムの制御」 第89回 日本細菌学会総会 2016.3.23

    髙橋 大輔長谷 耕二

    第89回 日本細菌学会総会, 

    2016年03月

    口頭発表(招待・特別)

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競争的研究費の研究課題 【 表示 / 非表示

  • 腸内細菌を自己として認識するγδT17細胞による宿主-腸内細菌共生関係構築

    2023年04月
    -
    2025年03月

    2023年度 学術変革領域研究(A) (公募研究), 補助金,  研究代表者

  • ケミカルバイオロジーを利用した濾胞制御性T細胞分化機序の解明

    2020年04月
    -
    2025年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 高橋 大輔, 基盤研究(C), 補助金,  研究代表者

  • 腸内細菌が産生する酪酸による関節リウマチ抑制メカニズムの解明

    2017年04月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 高橋 大輔, 若手研究(B), 補助金,  研究代表者

  • 腸上皮と上皮間リンパ球の相互作用に基づく粘膜上皮層免疫システムの成立機構の解析

    2015年11月
    -
    2017年03月

    科学研究費補助金(文部科学省・日本学術振興会), 補助金,  研究代表者

 

担当授業科目 【 表示 / 非表示

  • 課題研究(生化学)

    2024年度

  • 細胞培養・遺伝子実験特別演習

    2024年度

  • 演習(生化学)

    2024年度

  • 卒業研究1(薬学科)

    2024年度

  • 高度研究機器特別演習

    2024年度

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