深谷 知宏 (フカヤ トモヒロ)

Fukaya Tomohiro

写真a

所属

医学部 医学科 感染症学講座免疫学分野

職名

助教

外部リンク

学位 【 表示 / 非表示

  • 博士(高次生命科学) ( 2011年3月   東京医科歯科大学 )

研究分野 【 表示 / 非表示

  • ライフサイエンス / 免疫学

 

論文 【 表示 / 非表示

  • Gut dysbiosis promotes the breakdown of oral tolerance mediated through dysfunction of mucosal dendritic cells 査読あり

    Fukaya T., Uto T., Mitoma S., Takagi H., Nishikawa Y., Tominaga M., Choijookhuu N., Hishikawa Y., Sato K.

    Cell Reports   42 ( 5 )   112431   2023年5月

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    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: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.

    DOI: 10.1016/j.celrep.2023.112431

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  • Spatiotemporal expression of HMGB2 regulates cell proliferation and hepatocyte size during liver regeneration 査読あり

    Yano K., Choijookhuu N., Ikenoue M., Fidya , Fukaya T., Sato K., Lee D., Taniguchi N., Chosa E., Nanashima A., Hishikawa Y.

    Scientific Reports   12 ( 1 )   11962   2022年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    Liver regeneration is an extraordinarily complex process involving a variety of factors; however, the role of chromatin protein in hepatocyte proliferation is largely unknown. In this study, we investigated the functional role of high-mobility group box 2 (HMGB2), a chromatin protein in liver regeneration using wild-type and HMGB2-knockout (KO) mice. Liver tissues were sampled after 70% partial hepatectomy (PHx), and analyzed by immunohistochemistry, western blotting and flow cytometry using various markers of cell proliferation. In WT mice, hepatocyte proliferation was strongly correlated with the spatiotemporal expression of HMGB2; however, cell proliferation was significantly delayed in hepatocytes of HMGB2-KO mice. Quantitative PCR demonstrated that cyclin D1 and cyclin B1 mRNAs were significantly decreased in HMGB2-KO mice livers. Interestingly, hepatocyte size was significantly larger in HMGB2-KO mice at 36–72 h after PHx, and these results suggest that hepatocyte hypertrophy appeared in parallel with delayed cell proliferation. In vitro experiments demonstrated that cell proliferation was significantly decreased in HMGB2-KO cells. A significant delay in cell proliferation was also found in HMGB2-siRNA transfected cells. In summary, spatiotemporal expression of HMGB2 is important for regulation of hepatocyte proliferation and cell size during liver regeneration.

    DOI: 10.1038/s41598-022-16258-4

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  • Congenital Deficiency of Conventional Dendritic Cells Promotes the Development of Atopic Dermatitis-Like Inflammation 査読あり 国際共著

    Nishikawa Y., Fukaya T., Fukui T., Uto T., Takagi H., Nasu J., Miyanaga N., Riethmacher D., Choijookhuu N., Hishikawa Y., Amano M., Sato K.

    Frontiers in Immunology   12   712676   2021年7月

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    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:Frontiers in Immunology  

    Atopic dermatitis (AD) is a common pruritic inflammatory skin disease characterized by impaired epidermal barrier function and dysregulation of Thelper-2 (TH2)-biased immune responses. While the lineage of conventional dendritic cells (cDCs) are implicated to play decisive roles in T-cell immune responses, their requirement for the development of AD remains elusive. Here, we describe the impact of the constitutive loss of cDCs on the progression of AD-like inflammation by using binary transgenic (Tg) mice that constitutively lacked CD11chi cDCs. Unexpectedly, the congenital deficiency of cDCs not only exacerbates the pathogenesis of AD-like inflammation but also elicits immune abnormalities with the increased composition and function of granulocytes and group 2 innate lymphoid cells (ILC2) as well as B cells possibly mediated through the breakdown of the Fms-related tyrosine kinase 3 ligand (Flt3L)-mediated homeostatic feedback loop. Furthermore, the constitutive loss of cDCs accelerates skin colonization of Staphylococcus aureus (S. aureus), that associated with disease flare. Thus, cDCs maintains immune homeostasis to prevent the occurrence of immune abnormalities to maintain the functional skin barrier for mitigating AD flare.

    DOI: 10.3389/fimmu.2021.712676

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  • Essential role of submandibular lymph node dendritic cells in protective sublingual immunotherapy against murine allergy 査読あり

    Miyanaga N., Takagi H., Uto T., Fukaya T., Nasu J., Fukui T., Nishikawa Y., Sparwasser T., Choijookhuu N., Hishikawa Y., Nakamura T., Tono T., Sato K.

    Communications Biology   3 ( 1 )   742   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Communications Biology  

    While sublingual immunotherapy (SLIT) is known as an allergen-specific treatment for type-1 allergies, how it controls allergic pathogenesis remains unclear. Here, we show the prerequisite role of conventional dendritic cells in submandibular lymph nodes (ManLNs) in the effectiveness of SLIT for the treatment of allergic disorders in mice. Deficiency of conventional dendritic cells or CD4+Foxp3+ regulatory T (Treg) cells abrogates the protective effect of SLIT against allergic disorders. Furthermore, sublingual antigenic application primarily induces antigen-specific CD4+Foxp3+ Treg cells in draining ManLNs, in which it is severely impaired in the absence of cDCs. In ManLNs, migratory CD11b+ cDCs are superior to other conventional dendritic cell subsets for the generation of antigen-specific CD4+Foxp3+ Treg cells, which is reflected by their dominancy in the tolerogenic features to favor this program. Thus, ManLNs are privileged sites in triggering mucosal tolerance mediating protect effect of SLIT on allergic disorders that requires a tolerogenesis of migratory CD11b+ conventional dendritic cells.

    DOI: 10.1038/s42003-020-01466-3

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  • Pivotal role of carbohydrate recognition domain in self-interaction of CLEC4A to elicit the ITIM-mediated inhibitory function in murine conventional dendritic cells in vitro. 査読あり

    Nasu J, Uto T, Fukaya T, Takagi H, Fukui T, Miyanaga N, Nishikawa Y, Yamasaki S, Yamashita Y, Sato K

    International immunology   32 ( 10 )   673 - 682   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/intimm/dxaa034

    PubMed

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書籍等出版物 【 表示 / 非表示

  • Current Topics in Microbiology and Immunology

    Sato, K. Uto, T., Fukaya, T., and Takagi, H.( 担当: 共著 ,  範囲: Regulatory dendritic cells)

    Springer Publishing  2017年9月 

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    記述言語:英語 著書種別:学術書

  • Methods in Molecular Biology

    Fukaya, T., Takagi, H., Uto, T, Arimura, K., and Sato, K.( 担当: 共著 ,  範囲: Analysis of DC functions using CD205-DTR knock-in mice)

    Springer Publishing  2016年5月 

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    記述言語:英語 著書種別:学術書

MISC 【 表示 / 非表示

  • 樹状細胞のはたらき②pDCsによる免疫応答制御 招待あり

    宇都倫史•深谷知宏•三苫修也•佐藤克明

    VIP   ( 31 )   2 - 7   2023年7月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

  • 樹状細胞のはたらき①樹状細胞亜集団と免疫応答制御 招待あり

    宇都倫史•深谷知宏•三苫修也•佐藤克明

    VIP   ( 30 )   32 - 38   2023年4月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

  • 樹状細胞を標的とした免疫チェックポイント阻害療法

    宇都倫史•深谷知宏•三苫修也•佐藤克明.

    腫瘍内科   31 ( 3 )   300 - 306   2023年1月

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    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)  

  • 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1月

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    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)  

  • Author Correction: Pivotal role of CD103 in the development of psoriasiform dermatitis (Scientific Reports, (2020), 10, 1, (8371), 10.1038/s41598-020-65355-9)

    Fukui T., Fukaya T., Uto T., Takagi H., Nasu J., Miyanaga N., Nishikawa Y., Koseki H., Choijookhuu N., Hishikawa Y., Yamashita Y., Sato K.

    Scientific Reports   10 ( 1 )   16375   2020年12月

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    記述言語:日本語   出版者・発行元:Scientific Reports  

    This Article contains errors in the Methods section, under the subheading ‘Generation of Cd103-/- mice’, “The linearized targeting construct was introduced by electroporation into C57BL/6-derived JN/2 recombinant embryonic stem cell (ESC) and neomycin-resistant clones were first screened for homologous recombination by PCR utilizing a pair of the following oligonucleotides: Primer 1 (5'-ATA TGT AGT GTC TGG TCA GGA TAA TAG TTG-3') and Primer 2 (5'-ATA ACC TCC TCT CCT ATG GTA CCT AAA C-3').” should read: “The linearized targeting construct was introduced by electroporation into C57BL/6-derived JN/2 recombinant embryonic stem cell (ESC) and neomycin-resistant clones were first screened for homologous recombination by PCR utilizing a pair of the following oligonucleotides: Primer 1 (5'-ATA TGT AGT GTC TGG TCA GGA TAA TAG TTG-3') and Primer 3 (5'-ATA ACC TCC TCT CCT ATG GTA CCT AAA C-3').” “Transmission of the targeted allele was confirmed by PCR with Primer 1 and Primer 3 (5'-CTT TAT ATT TCA TTT TTG CTC AGG CTT C-3'). The mutant mice were cross-mated for more than nine generations with B6.FLIP mice to excise the flanked FRT sites by Flp-recombinase, and 8- to 12-week-old Cd103+/+ littermates were used as WT mice. Then, Cd103+/- littermates were crossed to obtain homozygotes, and transmission of the targeted allele was confirmed by PCR with Primer 1 and Primer 3.” should read: “Transmission of the targeted allele was confirmed by PCR with Primer 1 and Primer 2 (5'-CTT TAT ATT TCA TTT TTG CTC AGG CTT C-3'). The mutant mice were cross-mated for more than nine generations with B6.FLIP mice to excise the flanked FRT sites by Flp-recombinase, and 8- to 12-week-old Cd103+/+ littermates were used as WT mice. Then, Cd103+/- littermates were crossed to obtain homozygotes, and transmission of the targeted allele was confirmed by PCR with Primer 1 and Primer 2”.

    DOI: 10.1038/s41598-020-71156-x

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講演・口頭発表等 【 表示 / 非表示

  • DCIR2 is an immune regulatory molecule expressed on conventional dendritic cells to suppress tumor immunity 国際会議

    Uto T, Tominaga M, Fukaya T, Mitoma S, Sato K.

    JSICR/MMCB 2023 Joint Symposium  (Ito International Research Center, University of Tokyo)  2023年5月25日 

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    開催年月日: 2023年5月25日 - 2023年5月26日

    記述言語:英語   会議種別:ポスター発表  

    開催地:Ito International Research Center, University of Tokyo  

  • Congenital deficiency of conventional dendritic cells promotes the development of atopic dermatitis-like inflammation 国際会議

    Mitoma S, Fukaya T, Uto T, Sato K.

    JSICR/MMCB 2023 Joint Symposium  (Ito International Research Center, University of Tokyo)  2023年5月25日 

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    開催年月日: 2023年5月25日 - 2023年5月26日

    記述言語:英語   会議種別:ポスター発表  

    開催地:Ito International Research Center, University of Tokyo  

  • CD103+ conventional dendritic cells play a critical role in the development of oral tolerance 国際会議

    Fukaya T, Uto T, Mitoma S, Tominaga M, Sato K.

    JSICR/MMCB 2023 Joint Symposium  (Ito International Research Center, University of Tokyo)  2023年5月25日 

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    開催年月日: 2023年5月25日 - 2023年5月26日

    記述言語:英語   会議種別:ポスター発表  

    開催地:Ito International Research Center, University of Tokyo  

  • 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、宇都倫史、冨永萌、佐藤克明

    第51回日本免疫学会総会  2022年12月7日 

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    開催年月日: 2022年12月7日 - 2022年12月9日

    記述言語:英語   会議種別:口頭発表(一般)  

  • Clec4A4 acts as negative immune checkpoint regulator expressed on conventional dendritic cells to suppress tumor immunity

    宇都倫史、冨永萌、深谷知宏、佐藤克明

    第51回日本免疫学会総会  2022年12月9日 

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    開催年月日: 2022年12月7日 - 2022年12月9日

    記述言語:英語   会議種別:口頭発表(一般)  

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受賞 【 表示 / 非表示

  • 第51回日本免疫学会学術集会 ベストポスター賞

    2022年12月   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

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    受賞区分:国内学会・会議・シンポジウム等の賞 

科研費(文科省・学振・厚労省)獲得実績 【 表示 / 非表示

  • 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

    研究課題/領域番号:23K06768  2023年04月 - 2026年03月

    科学研究費補助金  基盤研究(C)

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    担当区分:研究代表者 

  • 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

    2017年04月 - 2020年03月

    科学研究費補助金  若手研究(B)

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    担当区分:研究代表者 

  • 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

    2014年04月 - 2017年03月

    科学研究費補助金  若手研究(B)

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    担当区分:研究代表者 

    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

寄附金・講座・研究部門 【 表示 / 非表示

  • 2022年度ニッポンハム食の未来財団(B)個人研究助成

    寄附者名称:ニッポンハム食の未来財団 2022年04月

 

授業 【 表示 / 非表示

  • 環境と生命

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    科目区分:共通教育科目