Fukaya Tomohiro

写真a

Affiliation

Faculty of Medicine School of Medicine Department of Infectious Diseases, Immunology

Title

Assistant Professor

External Link

Degree 【 display / non-display

  • 博士(高次生命科学) ( 2011.3   東京医科歯科大学 )

Research Areas 【 display / non-display

  • Life Science / Immunology

 

Papers 【 display / non-display

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

    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   2022.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher: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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    PubMed

  • Congenital Deficiency of Conventional Dendritic Cells Promotes the Development of Atopic Dermatitis-Like Inflammation Reviewed

    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   2021.7

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher: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

    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   2020.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher: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. Reviewed

    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   2020.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/intimm/dxaa034

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  • Pivotal role of CD103 in the development of psoriasiform dermatitis Reviewed

    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 )   8371   2020.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Scientific Reports  

    © 2020, The Author(s). The integrin αE known as CD103 binds integrin β7 to form the complete heterodimeric integrin molecule αEβ7. CD103 is mainly expressed by lymphocytes within epithelial tissues of intestine, lung, and skin as well as subsets of mucosal and dermal conventional dendritic cells (cDCs). CD103 has been originally implicated in the attachment of lymphocytes to epithelium in the gut and skin through the interaction with E-cadherin expressed on intestinal epithelial cells, keratinocytes, and Langerhans cells (LCs). However, an impact of CD103 on the cutaneous immune responses and the development of inflammatory skin diseases remains elusive. Here, we report that CD103 regulates the development of psoriasiform dermatitis through the control of the function of cDCs. Deficiency in CD103 exacerbates psoriasiform dermatitis, accompanied by excessive epidermal hyperplasia and infiltration of inflammatory leukocytes. Furthermore, deficiency in CD103 not only accelerates the production of proinflammatory cytokines in psoriatic lesions but also promotes the generation of lymphocytes producing interleukin (IL)-17 in the skin-draining peripheral lymph nodes (PLNs). Under the deficiency in CD103, cDCs localized in PLNs enhance cytokine production following activation. Thus, our findings reveal a pivotal role for CD103 in the control of the function of cDCs to regulate cutaneous inflammation in psoriasiform dermatitis.

    DOI: 10.1038/s41598-020-65355-9

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Books 【 display / non-display

  • Current Topics in Microbiology and Immunology

    Sato, K. Uto, T., Fukaya, T., and Takagi, H.( Role: Joint author ,  Regulatory dendritic cells)

    Springer Publishing  2017.9 

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    Language:English Book type:Scholarly book

  • Methods in Molecular Biology

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

    Springer Publishing  2016.5 

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    Language:English Book type:Scholarly book

MISC 【 display / non-display

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

    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   2020.12

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (bulletin of university, research institution)   Publisher: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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  • 経口免疫寛容の誘導における形質細胞様樹状細胞の役割

    佐藤克明, 宇都倫史, 高木秀明, 深谷知宏

    臨床免疫・アレルギー科   71 ( 2 )   134 - 137   2019.2

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 樹状細胞サブセットによる免疫制御機構

    佐藤克明•宇都倫史•深谷知宏•高木秀明

    臨床免疫・アレルギー科   67 ( 6 )   539   2017.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 樹状細胞サブセットと免疫応答制御

    佐藤克明•宇都倫史•深谷知宏•高木秀明

    炎症と免疫   25 ( 3 )   71   2017.4

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  • 亜麻仁油の摂取は食物アレルギーを改善する? Invited

    深谷 知宏

    ファルマシア   52 ( 6 )   559 - 559   2016.6

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Presentations 【 display / non-display

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

    宇都倫史、深谷知宏、高木秀明、西川陽太郎、冨永萌、佐藤克明

    第50回日本免疫学会総会  2021.12.9 

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    Event date: 2021.12.8 - 2021.12.10

    Language:English   Presentation type:Oral presentation (general)  

  • Plasmacytoid dendritic cells potentiate an effective anti-tumor immunity by preventing T-cell exhaustion

    高木秀明、宇都倫史、深谷知宏、西川陽太郎、冨永萌、佐藤克明

    第50回日本免疫学会総会  2021.12.9 

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    Event date: 2021.12.8 - 2021.12.10

    Language:English   Presentation type:Poster presentation  

  • Gut dysbiosis abrogates the protective effect of oral tolerance through the dysfunction of CD103+ cDCs in mesenteric lymph nodes

    深谷知宏、宇都倫史、高木秀明、西川陽太郎、冨永萌、佐藤克明

    第50回日本免疫学会総会  2021.12.9 

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    Event date: 2021.12.8 - 2021.12.10

    Language:English   Presentation type:Poster presentation  

  • Requirement of gut mucosal plasmacytoid dendritic cells for establishing oral tolerance to prevent undesirable allergic disorders

    宇都倫史、高木秀明、深谷知宏、奈須遵太、福井丈仁、宮永宜明、西川陽太郎、佐藤克明

    第48回日本免疫学会総会  (静岡、アクトシティ浜松) 

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    Event date: 2019.12.11 - 2019.12.13

    Language:English   Presentation type:Poster presentation  

    Venue:静岡、アクトシティ浜松  

  • Pivotal role of CD103 expressed on conventional dendritic cells in the development of psoriasiform dermatitis through the regulation of cutaneous inflammation

    福井丈仁、深谷知宏、宇都倫史、高木秀明、奈須遵太、宮永宜明、西川陽太郎、佐藤克明

    第48回日本免疫学会総会  (静岡、アクトシティ浜松) 

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    Event date: 2019.12.11 - 2019.12.13

    Language:English   Presentation type:Poster presentation  

    Venue:静岡、アクトシティ浜松  

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Grant-in-Aid for Scientific Research 【 display / non-display

  • 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

    2017.04 - 2020.03

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

  • 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

    2014.04 - 2017.03

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

    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