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医学部 医学科 感染症学講座免疫学分野 |
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助教 |
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論文 【 表示 ／ 非表示 】
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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
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.
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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
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.
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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
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.
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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
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.
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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
書籍等出版物 【 表示 ／ 非表示 】
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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
記述言語：英語 著書種別：学術書
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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
記述言語：英語 著書種別：学術書
MISC 【 表示 ／ 非表示 】
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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
記述言語：日本語 掲載種別：記事・総説・解説・論説等（学術雑誌）
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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
記述言語：日本語 掲載種別：記事・総説・解説・論説等（学術雑誌）
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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
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）
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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
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）
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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
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”.
講演・口頭発表等 【 表示 ／ 非表示 】
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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
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
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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
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
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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
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
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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
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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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
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）
受賞 【 表示 ／ 非表示 】
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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
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 】
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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)
担当区分：研究代表者
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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)
担当区分：研究代表者
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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)
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