Multi Regulatory System for Gut Homeostasis and Inflammation

• Project/Area Number: 18H05280
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Review Section: Broad Section I
• Research Institution: The University of Tokyo
• Principal Investigator: 清野 宏 東京大学, 医科学研究所, 特任研究員 (10271032)
• Co-Investigator(Kenkyū-buntansha): 倉島 洋介 千葉大学, 大学院医学研究院, 准教授 (30729372)
• Project Period (FY): 2018-06-11 – 2023-03-31
• Project Status: Granted (Fiscal Year 2022)
• Budget Amount: ¥191,360,000 (Direct Cost: ¥147,200,000、Indirect Cost: ¥44,160,000); Fiscal Year 2022: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000); Fiscal Year 2021: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000); Fiscal Year 2020: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000); Fiscal Year 2019: ¥37,050,000 (Direct Cost: ¥28,500,000、Indirect Cost: ¥8,550,000); Fiscal Year 2018: ¥40,430,000 (Direct Cost: ¥31,100,000、Indirect Cost: ¥9,330,000)
• Keywords: 炎症性腸疾患 / 臓器連関 / 粘膜免疫 / 蠕動運動 / 抗菌ペプチド / パネート細胞 / 膵臓 / 間葉系細胞 / 陰窩 / 腸間膜脂肪

Outline of Annual Research Achievements

腸管粘膜は食餌性成分や腸内細菌叢の変動を感知することで組織恒常性を維持しているが、ひとたびその機能が破綻すると炎症性腸疾患をはじめとした慢性炎症が起こる。本研究は、炎症性腸疾患およびその合併症の病態形成機構の解明を目的としており、腸管粘膜を起点とした①「腸－膵連関」、②「粘膜―間葉系連関」、③「粘膜－筋連関」の3つの臓器・組織間相互作用についての研究課題を設けて取り組んでいる。
①「腸－膵連関」プロジェクトにおいては、膵臓から分泌される糖タンパクであるGlycoprotein 2(GP2)が一部の腸内細菌の線毛に結合することで腸内細菌の粘膜組織内への流入を抑制していることを見出し、報告に至った（Kurashima Y et al., Nat Commun 2021)。さらなる展開として、本年度はGP2結合菌の同定に向けた網羅的な解析を進めている。加えて、昨年度に続き膵臓による生体防御機構に関わる複数種の腸内細菌の同定に至っている。
②「粘膜―間葉系連関」プロジェクトでは、腸管の陰窩部ならびに粘膜下組織が粘膜上皮に及ぼす作用について、幹細胞のニッチに着目しニッチ形成・細胞増殖・分化に関わるWnt等のサイトカインの産生維持機構について解析を進めた。これらサイトカインを産生する細胞の同定を目的として、新たにマウス腸管陰窩を分離する手法を確立し、報告した(Matsumura S et al., Sci Rep 2020)。本報告ではWnt産生に関わる新たな受容体としてレプチン受容体を同定している。当受容体のリガンドを腸炎マウスに投与すると、粘膜バリア機能の維持に伴う腸炎の軽症化が見られた。
③「粘膜－筋層連関」プロジェクトでは、1細胞遺伝子解析による腸管筋層解析を実施し、昨年度に引き続き炎症時において炎症細胞の動員に関わる細胞集団の分類を進めた。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

本研究計画を構成する3つの研究プロジェクト共に、論文発表および再投稿準備中であることから、一定の研究成果が得られており、今後はこれまで得られた成果を統合することで新たな知見につながると考えられる。

Strategy for Future Research Activity

本研究では、腸管粘膜での炎症疾患およびその合併症の病態形成機構の解明に向けた基盤構築を目的に、①「腸－膵連関」、②「粘膜―間葉系連関」、③「粘膜－筋連関」の３つ項目について解析を進めている。それぞれの研究項目で見出された連関システムの破綻機序をモデル動物として作製し、最終的には得られた知見の融合を目指す。
これまでに得られた成果から、当初の予定通り3つの研究を結びつける段階に入っている。
①「腸－膵連関」プロジェクトでは、新たに膵臓の機能を制御する腸内細菌の同定を進め複数種の腸内細菌を同定しており、昨年度に継続し、腸内細菌移入実験等を中心に菌体成分・代謝物の同定に向けて取り組む。
②「粘膜―間葉系連関」プロジェクトにおいては、これまでマウス小腸陰窩部において抗菌ペプチドの産生を介して腸管恒常性維持に働くパネート細胞の機能が、自然・獲得免疫系の両方によって制御されることを見出している。パネート細胞の機能が腸管の微小環境・部位によって異なるというデータを得ており、微小環境の構成細胞の解析を進めることで新たなパネート細胞の機能制御機構を明らかにする。
③「粘膜－筋層連関」プロジェクトでは、1細胞遺伝子解析による筋層解析を実施しており、炎症シグナルが蠕動運動に及ぼす影響について、筋層を構成する細胞の機能破綻メカニズムを明らかにする。

Assessment Rating

Interim Assessment Comments (Rating)

A: In light of the aim of introducing the research area into the research categories, the expected progress has been made in research.

Research Products

• [Int'l Joint Research] NIAID NIH(米国)
• [Int'l Joint Research] Noguchi Memorial Institute/Ghana Health Service Institute/NIID(ガーナ)
• [Int'l Joint Research] UCSD/Hiroshima University/Chiba University(米国)
• [Int'l Joint Research] Universiti Sains Malaysia/Universidad de Concepcion, Chile/University of Tokyo(マレーシア)
• [Journal Article] Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy. (2021)
  • Author(s): Takasato Y, Kurashima Y, Kiuchi M, Hirahara K, Murasaki S, Arai F, Izawa K, Kaitani A, Shimada k, Saito Y, Toyoshima S, Nakamura M, Fujisawa K, Okayama Y, Kunisawa J, Kubo M, Takemura N, Uematsu S, Akira S, Kitaura J, Takahashi T, Nakayama T, Kiyono H
  • Journal Title: Mucosal Immunol. Volume: 14 Pages: 640-651
  • DOI: 10.1038/s41385-020-00358-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fecal Microbiome Composition in Healthy Adults in Ghana (2021)
  • Author(s): Parbie Prince Kofi、Mizutani Taketoshi、Ishizaka Aya、Kawana-Tachikawa Ai、Runtuwene Lucky Ronald、Seki Sayuri、Abana Christopher Zaab-Yen、Kushitor Dennis、Bonney Evelyn Yayra、Ofori Sampson Badu、Uematsu Satoshi、Imoto Seiya、Kimura Yasumasa、Kiyono Hiroshi、Ishikawa Koichi、Ampofo William Kwabena、Matano Tetsuro
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 74 Issue: 1 Pages: 42-47
  • DOI: 10.7883/yoken.jjid.2020.469 10.7883/yoken.JJID.2020.469
  • NAID: 130007973724
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lipopolysaccharide from Gut‐Associated Lymphoid‐Tissue‐Resident Alcaligenes faecalis : Complete Structure Determination and Chemical Synthesis of Its Lipid?A (2021)
  • Author(s): Shimoyama A、Di Lorenzo F、Yamaura H、Mizote K、Palmigiano A、Pither MD.、Speciale I、Uto T、Masui S、Sturiale L、Garozzo D、Hosomi K、Shibata N、Kabayama K、Fujimoto Y、Silipo A、Kunisawa Jun、Kiyono H、Molinaro A、Fukase K
  • Journal Title: Angew. Chem. Int. Ed. Engl Volume: 60 Pages: 10023-10031
  • DOI: 10.1002/anie.202012374
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enzymatically polymerised polyphenols prepared from various precursors potentiate antigen-specific immune responses in both mucosal and systemic compartments in mice (2021)
  • Author(s): Tada, R., Ogasawara, M., Yamanaka, D., Sakurai, Y., Negishi, Y., Kiyono, H., Ohno, N., Kunisawa, J. and Aramaki, Y.
  • Journal Title: PLoS One Volume: eCollection 16(2)
  • DOI: 10.1371/journal.pone.0246422
  • Peer Reviewed / Open Access
• [Journal Article] Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation (2021)
  • Author(s): Fujimoto, Kosuke, et al.
  • Journal Title: Gastroenterology. Volume: - Pages: 400-405
  • DOI: 10.1053/j.gastro.2021.02.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation (2021)
  • Author(s): Kurashima Yosuke、Kigoshi Takaaki、Murasaki Sayuri、Arai Fujimi、Shimada Kaoru、Seki Natsumi、Kim Yun-Gi、Hase Koji、Ohno Hiroshi、Kawano Kazuya、Ashida Hiroshi、Suzuki Toshihiko、Morimoto Masako、Saito Yukari、Sasou Ai、Goda Yuki、Yuki Yoshikazu、Inagaki Yutaka、Iijima Hideki、Suda Wataru、Hattori Masahira
  • Journal Title: Nat. Commun Volume: 12 Pages: 1067-1067
  • DOI: 10.1038/s41467-021-21277-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct Age-Specific miRegulome Profiling of Isolated Small and Large Intestinal Epithelial Cells in Mice (2021)
  • Author(s): Lee Juneyoung、Mohsen Attayeb、Banerjee Anik、McCullough Louise D.、Mizuguchi Kenji、Shimaoka Motomu、Kiyono Hiroshi、Park Eun Jeong
  • Journal Title: Int J Mol Sci Volume: 22 Pages: 3544-3544
  • DOI: 10.3390/ijms22073544
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparative whole-genome and proteomics analyses of the next seed bank and the original master seed bank of MucoRice-CTB 51A line, a rice-based oral cholera vaccine (2021)
  • Author(s): Sasou Ai、Yuki Yoshikazu、Honma Ayaka、Sugiura Kotomi、Kashima Koji、Kozuka-Hata Hiroko、Nojima Masanori、Oyama Masaaki、Kurokawa Shiho、Maruyama Shinichi、Kuroda Masaharu、Tanoue Shinjiro、Takamatsu Narushi、Fujihashi Kohtaro、Goto Eiji、Kiyono Hiroshi
  • Journal Title: Lancet Microbial Volume: 22 Pages: 59-59
  • DOI: 10.1186/s12864-020-07355-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon. (2020)
  • Author(s): Junya Isobe, Shintarou Maeda, Yuuki Obata, Keito Iizuka, Yutaka Nakamura, Yumiko Fujimura, Tatsuki Kimizuka, Kouya Hattori, Yun-Gi Kim, Tatsuya Morita, Ikuo Kimura, Stefan Offermanns, Takahiro Adachi, Atsuhito Nakao, Hiroshi Kiyono, Daisuke Takahashi, Koji Hase
  • Journal Title: Int. Immunol. Volume: 32 Pages: 243-258
  • DOI: 10.1093/intimm/dxz078
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fatty Acid Metabolism in the Host and Commensal Bacteria for the Control of Intestinal Immune Responses and Diseases (2020)
  • Author(s): Hosomi K, Kiyono H, Kunisawa J.
  • Journal Title: Gut Microbes. Volume: 23 Pages: 1-1
  • DOI: 10.1080/19490976.2019.1612662
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A heterodimeric antibody fragment for passive immunotherapy against norovirus infection (2020)
  • Author(s): Yuki Yoshikazu、Kurokawa Shiho、Sato Shintaro、Sasou Ai、Matsumoto Naomi、Suzuki Akio、Sakon Naomi、Goda Yuki、Takeyama Natsumi、Miyoshi Tatsuya、Marcotte Harold、Tanaka Tomoyuki、Hammarstrom Lennart、Kiyono Hiroshi
  • Journal Title: J Infect Dis Volume: － Pages: 470-478
  • DOI: 10.1093/infdis/jiaa115
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Microfold cell-dependent antigen transport alleviates infectious colitis by inducing antigen-specific cellular immunity (2020)
  • Author(s): Nakamura Yutaka、Mimuro Hitomi、Kunisawa Jun、Furusawa Yukihiro、Takahashi Daisuke、Fujimura Yumiko、Kaisho Tsuneyasu、Kiyono Hiroshi、Hase Koji
  • Journal Title: Mucosal Immunol Volume: in press Pages: 679-690
  • DOI: 10.1038/s41385-020-0263-0
  • Peer Reviewed / Open Access
• [Journal Article] Adjuvant Activity of Synthetic Lipid A of Alcaligenes, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic Vaccine (2020)
  • Author(s): Wang Yunru、Hosomi Koji、Shimoyama Atsushi、Yoshii Ken、Yamaura Haruki、Nagatake Takahiro、Nishino Tomomi、Kiyono Hiroshi、Fukase Koichi、Kunisawa Jun
  • Journal Title: Vaccines Volume: 8 Pages: 395-395
  • DOI: 10.3390/vaccines8030395
  • Peer Reviewed / Open Access
• [Journal Article] Chemically Synthesized Alcaligenes Lipid A Shows a Potent and Safe Nasal Vaccine Adjuvant Activity for the Induction of Streptococcus pneumoniae-Specific IgA and Th17 Mediated Protective Immunity (2020)
  • Author(s): Yoshii Ken、Hosomi Koji、Shimoyama Atsushi、Wang Yunru、Yamaura Haruki、Nagatake Takahiro、Suzuki Hidehiko、Lan Huangwenxian、Kiyono Hiroshi、Fukase Koichi、Kunisawa Jun
  • Journal Title: Microorganisms Volume: 8 Pages: 1102-1102
  • DOI: 10.3390/microorganisms8081102
  • Peer Reviewed / Open Access
• [Journal Article] Maternal omega-3 docosapentaenoic acid inhibits infant allergic dermatitis through TRAIL-expressing plasmacytoid dendritic cells in mice (2020)
  • Author(s): Hirata SI, Nagatake T, Sawane K, Hosomi K, Honda T, Ono S, Shibuya N, Saito E, Adachi J, Abe Y, Isoyama J, Suzuki H, Matsunaga A, Tomonaga T, Kiyono H, Kabashima K, Arita M, and Kunisawa J
  • Journal Title: Allergy Volume: - Pages: 0-0
  • DOI: 10.1111/all.14217
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metagenome Data on Intestinal Phage-Bacteria Associations Aids the Development of Phage Therapy against Pathobionts (2020)
  • Author(s): Fujimoto Kosuke、Kimura Yasumasa、Shimohigoshi Masaki、Satoh Takeshi、Sato Shintaro、Tremmel Georg、Uematsu Miho、Kawaguchi Yunosuke、Usui Yuki、Nakano Yoshiko、Hayashi Tetsuya、Kashima Koji、Yuki Yoshikazu、Yamaguchi Kiyoshi、Furukawa Yoichi、Kakuta Masanori、Akiyama Yutaka、Yamaguchi Rui、Crowe Sheila E. et al
  • Journal Title: Cell Host Microbe Volume: 28 Pages: 380-389
  • DOI: 10.1016/j.chom.2020.06.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lymphoid Tissue Resident Alcaligenes Establish an Intracellular Symbiotic Environment by Creating a Unique Energy Shift in Dendritic Cells (2020)
  • Author(s): Hosomi Koji、Shibata Naoko、Shimoyama Atsushi、Uto Tomoya、Nagatake Takahiro、Tojima Yoko、Nishino Tomomi、Takeyama Haruko、Fukase Koichi、Kiyono Hiroshi、Kunisawa Jun
  • Journal Title: Front Microbiol Volume: 11 Pages: 1-10
  • DOI: 10.3389/fmicb.2020.561005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The global response to the COVID-19 pandemic: how have immunology societies contributed? (2020)
  • Author(s): Osier, F., Ting, J., Fraser, J., Lambrecht B, Romano, M., Gazzinelli, R., Bortoluci, K., Zamboni, D., Akbar, A., Evans, J., Brown, D., Patel, K., Wu, Y., Perez, A., Perez, O., Kamradt, T., Falk, C., Barda-Saad, M., Ariel, A., Santoni, A., Annunziato, F., Cassatella, M. Kiyono, H., els.
  • Journal Title: Nat Rev Immunol Volume: 10 Pages: 594-602
  • DOI: 10.1038/s41577-020-00428-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stratified layer analysis reveals intrinsic leptin stimulates cryptal mesenchymal cells for controlling mucosal inflammation (2020)
  • Author(s): Matsumura Seiichi、Kurashima Yosuke、Murasaki Sayuri、Morimoto Masako、Arai Fujimi、Saito Yukari、Katayama Nana、Kim Dayoung、Inagaki Yutaka、Kudo Takahiro、Ernst Peter B.、Shimizu Toshiaki、Kiyono Hiroshi
  • Journal Title: Sci Rep Volume: 10 Pages: 18351-18351
  • DOI: 10.1038/s41598-020-75186-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 粘膜免疫の今昔そして未来へ (2020)
  • Author(s): Fujihashi, K. and Kiyono, H.
  • Journal Title: 感染・炎症・免疫 Volume: 50-2 Pages: 116-138
  • Open Access
• [Journal Article] 腸内細菌と炎症性腸疾患 (2020)
  • Author(s): Shibata, N. and Kiyono, H.
  • Journal Title: Pharma Medica Volume: 38(12) Issue: 12 Pages: 17-22
  • DOI: 10.34449/J0001.38.12_0017-0022
  • ISSN: 0289-5803
  • Open Access
• [Journal Article] Persistent colonization of non-lymphoid tissue-resident macrophages by Stenotrophomonas maltophilia (2020)
  • Author(s): Takahashi Ichiro, Hosomi Koji, Nagatake Takahiro, Tobou Hirokazu, Yamamoto Daiki, Hayashi Ikue, Kurashima Yosuke, Sato Shintaro, Shibata Naoko, Goto Yoshiyuki, Maruyama Fumito, Nakagawa Ichiro, Kuwae Asaomi, Abe Akio, Kunisawa Jun, Kiyono Hiroshi
  • Journal Title: Int. Immunol. Volume: 32 Pages: 133-133
  • DOI: 10.1093/intimm/dxz071
  • NAID: 120006888456
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A role for the CCR5?CCL5 interaction in the preferential migration of HSV-2-specific effector cells to the vaginal mucosa upon nasal immunization (2019)
  • Author(s): Joo Sunyi、Suwanto Aldina、Sato Ayuko、Nakahashi-Ouchida Rika、Mori Hiromi、Uchida Yohei、Sato Shintaro、Kurashima Yosuke、Yuki Yoshikazu、Fujihashi Kohtaro、Kawaguchi Yasushi、Kiyono Hiroshi
  • Journal Title: Mucosal Immunol. Volume: 12 Pages: 1391-1403
  • DOI: 10.1038/s41385-019-0203-z
  • Peer Reviewed / Open Access
• [Journal Article] Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis (2019)
  • Author(s): Nishida K, Hasegawa A, Yamasaki S, Uchida R, Ohashi W, Kurashima Y, Kunisawa J, Kimura S, Iwanaga T, Watarai H, Hase K, Ogura H, Nakayama M, Kashiwakura J, Okayama Y, Kubo M, Ohara O, Kiyono H, Koseki H, Murakami M, Hirano T
  • Journal Title: Sci. Rep. Volume: 9 Pages: 10842-10842
  • DOI: 10.1038/s41598-019-47132-5
  • Peer Reviewed / Open Access
• [Journal Article] Antigen-Specific Mucosal Immunity Regulates Development of Intestinal Bacteria-Mediated Diseases (2019)
  • Author(s): Fujimoto Kosuke、Kawaguchi Yunosuke、Shimohigoshi Masaki、Gotoh Yoshiyuki、Nakano Yoshiko、Usui Yuki、Hayashi Tetsuya、Kimura Yasumasa、Uematsu Miho、Yamamoto Takuya、Akeda Yukihiro、Rhee Joon Haeng、Yuki Yoshikazu、Ishii Ken J.、Crowe Sheila E.、Ernst Peter B.、Kiyono Hiroshi、Uematsu Satoshi
  • Journal Title: Gastroenterology. Volume: 157 Pages: 1530-1543
  • DOI: 10.1053/j.gastro.2019.08.021
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Autonomous regulation of immunoglobulin E-mediated mast cell degranulation and immediate hypersensitivity reaction by an inhibitory receptor CD300a. (2019)
  • Author(s): Noval Rivas M, Wakita D, Franklin MK, Carvalho TT, Abolhesn A, Gomez AC, Fishbein MC, Chen S, Lehman TJ, Sato K, Shibuya A, Fasano A, Kiyono H, Abe M, Tatsumoto N, Yamashita M, Crother TR, Shimada K, Arditi M
  • Journal Title: Immunity Volume: 51(3) Pages: 508-521
  • DOI: 10.1016/j.immuni.2019.05.021
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Fucosyltransferase 2 induces lung epithelial fucosylation and exacerbates house dust mite-induced airway inflammation. (2019)
  • Author(s): Saku A, Hirose K, Ito T, Iwata A, Sato T, Kaji H, Tamachi T, Suto A, Goto Y, Domino SE, Narimatsu H, Kiyono H, Nakajima H
  • Journal Title: J. Allergy. Clin. Immunol. Volume: 144(3) Pages: 698-709
  • DOI: 10.1016/j.jaci.2019.05.010
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Distinct Roles for Peyer’s Patch B Cells for Induction of Antigen-specific IgA Antibody Responses in Mice Administered Oral Recombinant Salmonella (2019)
  • Author(s): Hashizume-Takizawa Tomomi、Shibata Naoko、Kurashima Yosuke、Kiyono Hiroshi、Kurita-Ochiai Tomoko、Fujihashi Kohtaro
  • Journal Title: Int. Immunol. Volume: - Pages: 531-541
  • DOI: 10.1093/intimm/dxz029
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dietary coconut oil ameliorates skin contact hypersensitivity through mead acid production in mice (2019)
  • Author(s): Tiwari Prabha、Nagatake Takahiro、Hirata So‐ichiro、Sawane Kento、Saika Azusa、Shibata Yuki、Morimoto Sakiko、Honda Tetsuya、Adachi Jun、Abe Yuichi、Isoyama Junko、Tomonaga Takeshi、Kiyono Hiroshi、Kabashima Kenji、Kunisawa Jun
  • Journal Title: Allergy Volume: NA Pages: 1522-1532
  • DOI: 10.1111/all.13762
  • Peer Reviewed
• [Journal Article] Human Norovirus Propagation in Human Induced Pluripotent Stem Cell?Derived Intestinal Epithelial Cells (2019)
  • Author(s): Sato Shintaro、Hisaie Kota、Kurokawa Shiho、Suzuki Akio、Sakon Naomi、Uchida Yohei、Yuki Yoshikazu、Kiyono Hiroshi
  • Journal Title: Cell. Mol. Gastro. Hepatol. Volume: 7 Pages: 164-4
  • DOI: 10.1016/j.jcmgh.2018.11.001
  • Peer Reviewed / Open Access
• [Journal Article] Polymeric Caffeic Acid Is a Safer Mucosal Adjuvant That Augments Antigen-Specific Mucosal and Systemic Immune Responses in Mice (2019)
  • Author(s): Tada Rui、Yamanaka Daisuke、Ogasawara Miki、Saito Momoko、Ohno Naohito、Kiyono Hiroshi、Kunisawa Jun、Aramaki Yukihiko
  • Journal Title: Mol. Pharm. Volume: 15 Pages: 4226-4234
  • DOI: 10.1021/acs.molpharmaceut.8b00648
  • Peer Reviewed
• [Journal Article] Intrinsic Control of Surface Immune and Epithelial Homeostasis by Tissue-Resident Gut Stromal Cells (2019)
  • Author(s): Kurashima Yosuke、Tokuhara Daisuke、Kamioka Mariko、Inagaki Yutaka、Kiyono Hiroshi
  • Journal Title: Front. Immunol. Volume: 10 Pages: 01281-01281
  • DOI: 10.3389/fimmu.2019.01281
  • Peer Reviewed / Open Access
• [Journal Article] New trends in mucosal immunology and allergy (2019)
  • Author(s): Kiyono, H. Izuhara, K.
  • Journal Title: Allergol. Int. Volume: 68.1 Issue: 1 Pages: 1-3
  • DOI: 10.1016/j.alit.2018.12.002
  • NAID: 130007557931
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] A comprehensive understanding of the gut mucosal immune system in allergic inflammation (2019)
  • Author(s): Tokuhara Daisuke、Kurashima Yosuke、Kamioka Mariko、Nakayama Toshinori、Ernst Peter、Kiyono Hiroshi
  • Journal Title: Allergol. Int. Volume: 68 Issue: 1 Pages: 17-25
  • DOI: 10.1016/j.alit.2018.09.004
  • NAID: 130007557958
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Current status and future directions of study on glycosylation for gut microbiota and the mucosal immune network. (2019)
  • Author(s): Goto, Y., Kiyono, H.
  • Journal Title: Glycoscience: Basic Science to Applications - Insights from the Japan Consortium. Volume: Mar2019 Pages: 92-94
• [Journal Article] Development of immune and microbial environment is independently regulated in the mammary gland (2018)
  • Author(s): Niimi K, Usami K, Fujita Y, Abe M, Furukawa M, Suyama Y, Sakai Y, Kamioka M, Shibata N, Park EJ, Sato S, Kiyono H, Yoneyama H, Kitazawa H, Watanabe K, Nochi T, Aso H
  • Journal Title: Mucosal Immunol Volume: 印刷中 Pages: 643-653
  • DOI: 10.1038/mi.2017.90
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Lymphoid tissue-resident Alcaligenes LPS induces IgA production without excessive inflammatory responses via weak TLR4 agonist activity (2018)
  • Author(s): N. Shibata, J. Kunisawa, K. Hosomi, Y. Fujimoto, K. Mizote, N. Kitayama, A. Shimoyama, H. Mimuro, S. Sato, N. 5 Kishishita, K. J. Ishii, K. Fukase, and H. Kiyono
  • Journal Title: Mucosal Immunol Volume: － Pages: 693-702
  • DOI: 10.1038/mi.2017.103
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 17,18-EpETE-GPR40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques (2018)
  • Author(s): Nagatake T, Shiogama Y, Inoue A, Kikuta J, Honda T, Tiwari P, Kishi T, Yanagisawa A, Isobe Y, Matsumoto N, Shimojou M, Morimoto S, Suzuki H, Hirata S, Steneberg P, Edlund H, Aoki J, Arita M, Kiyono H, Yasutomi Y, Ishii M, Kabashima K, Kunisawa J
  • Journal Title: J Allergy Clin Immunol. Volume: S0091-6749 Pages: 32949-32944
  • DOI: 10.1016/j.jaci.2017.09.053
  • NAID: 40021650879
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ATP as a Pathophysiologic Mediator of Bacteria-Host Crosstalk in the Gastrointestinal Tract (2018)
  • Author(s): Inami Akie、Kiyono Hiroshi、Kurashima Yosuke
  • Journal Title: Int J Mol Sci. Volume: 19 Pages: 2371-2371
  • DOI: 10.3390/ijms19082371
  • Peer Reviewed / Open Access
• [Journal Article] 共生と排除を司る粘膜マスト細胞 (2018)
  • Author(s): 倉島洋介
  • Journal Title: 腸内細菌学雑誌 Volume: 32 Pages: 159-166
  • NAID: 130007501993
• [Presentation] Pancreatic-Gut Axis for the Mucosal Protection (2021)
  • Author(s): Kurashima, Y.
  • Organizer: Joint Webinar of ‘Chiba University Tenure Track Seminar Program and International Research and Development Center for Mucosal Vaccines (IMSUT) Vaccine Center Seimnar
  • Invited
• [Presentation] 共生細菌による粘膜免疫制御 (2021)
  • Author(s): Kiyono, H.
  • Organizer: Nagasaki Intestinal Microbiology Study Group Webinar
  • Invited
• [Presentation] Considering Vaccination (2021)
  • Author(s): Kiyono, H.
  • Organizer: SMBC Nikko Securities Inc.’s Economic and Science Webinar, “Acknowledge COVID-19 correctly,”
  • Invited
• [Presentation] 腸内細菌の制御を担う新たな「膵臓」の役割 (2020)
  • Author(s): 倉島 洋介
  • Organizer: 第24回腸内細菌学会（誌上開催）
  • Invited
• [Presentation] 骨免疫学と粘膜免疫学の接点：そこから生まれるイノベーション (2020)
  • Author(s): 清野宏
  • Organizer: The 17th Osteoimmunology Forum
  • Invited
• [Presentation] 粘膜免疫を基盤とした予防・治療戦略 (2019)
  • Author(s): 清野宏
  • Organizer: 第６回アレルギー講習会
  • Invited
• [Presentation] 次世代型粘膜ワクチンによる感染症予防・治療戦略 (2019)
  • Author(s): 清野宏
  • Organizer: 第34階日本国際保健医療学会学術大会
  • Invited
• [Presentation] Fruitful collaboration between Ghana and Japan for SATREPS to mucosal vaccine development (2019)
  • Author(s): 清野宏
  • Organizer: The symposium for the 40th anniversary of Noguchi Memorial Institute, Accra, Ghana
  • Int'l Joint Research
• [Presentation] Introduction of cMAV Research Project (2019)
  • Author(s): 清野宏
  • Organizer: 千葉大創立70周年記念シンポジウム
• [Presentation] Mucosal multi-immunological ecological system to vaccine development (2019)
  • Author(s): 清野宏
  • Organizer: NIH-Japan-JSPS Symposium, Maryland, USA
  • Int'l Joint Research / Invited
• [Presentation] 粘膜免疫学創生から径鼻粘膜ワクチン開発へ (2019)
  • Author(s): 清野宏
  • Organizer: 第55回日本移植学会総会
  • Invited
• [Presentation] Intratissue commensal bacteria mediates balancing act between gut symbiosis and inflammation (2019)
  • Author(s): 清野宏
  • Organizer: The 10th Probiotics, Prebiotics and New foods, Nutraceuticals and Botanicals for Nutrition and Human and Microbiota Health/1st Science and Business Symposium, Rome, Itally
  • Int'l Joint Research / Invited
• [Presentation] Mucosal multi-ecological system for symbiosis, inflammation and vaccine (2019)
  • Author(s): 清野宏
  • Organizer: University of Bari, Medical Center, Bari, Italy
  • Int'l Joint Research / Invited
• [Presentation] 粘膜免疫：共生と排除、そしてワクチンへ (2019)
  • Author(s): 清野宏
  • Organizer: 第34回日本ショック学会
  • Invited
• [Presentation] 次世代型粘膜ワクチンによる感染症予防・治療戦略 (2019)
  • Author(s): 清野宏
  • Organizer: 第13回緩和医療薬学会年会講演会
  • Invited
• [Presentation] 粘膜免疫学創生から未来型ワクチン開発へ (2019)
  • Author(s): 清野宏
  • Organizer: 第120回日本耳鼻咽喉科学会学術講演会
  • Invited
• [Presentation] Orally-desensitized mast cells acquired regulatory characteristics for the control of allergy (2019)
  • Author(s): Kurashima, Y.
  • Organizer: 3rd Annual Symposium for the Center for Mucosal Immunology, Allergy and Vaccine Development
  • Int'l Joint Research
• [Presentation] The Mucosal Immune System for Symbiosis, Elimination and Vaccine (2019)
  • Author(s): Kiyono, H.
  • Organizer: Interdisciplinary Seminar on Mucosal Immunology at Tohoku University.
• [Presentation] Mesenchymal-myeloid cell interactions in microenvironment for novel fibrogenic machinery in tissue fibrosis (2019)
  • Author(s): Kurashima, Y., Murasaki, S., Morimoto, M., Shimizu, K., Kiyono, H.
  • Organizer: 第3回千葉大学グローバルプロミネント研究基幹シンポジウム
• [Presentation] Gut-multi Ecosystem for Immunity, Inflammation and Vaccine (2018)
  • Author(s): Kiyono, H.
  • Organizer: UCSD Gastroenterology Tuesday Morning Conference, San Diego, CA, USA
  • Invited
• [Presentation] Metagenome Analysis; Great Impact on the Next-Generation Surveillance System for Diarrheal and HIV Diseases (2018)
  • Author(s): Kiyono, H.
  • Organizer: Noguchi Hideyo Memorial Museum, Symposium on Infectious Disease and Immunity,
  • Int'l Joint Research / Invited
• [Presentation] Mucosal Equilibrium of Immunity and Symbiosis: From Basic to Vaccine Development (2018)
  • Author(s): Kiyono, H.
  • Organizer: University of Florida, Florida, USA
  • Int'l Joint Research / Invited
• [Presentation] Mucosal Multi-Ecological Loop of Intra- and Extra-Tissue Commensal Microbiota, Epithelial Cells and Immune Cells for Gut Homeostasis and InflammationMucosal Multi-Ecological Loop of Intra- and Extra-Tissue Commensal Microbiota, Epithelial Cells and Immune Cells for Gut Homeostasis and Inflammation (2018)
  • Author(s): Kiyono, H.
  • Organizer: TOLLerant final event "Microbiota/host dialogue, the molecular language”
  • Invited
• [Presentation] “Mucosal Immunology: Mucosal Homeostasis, Development of Novel Oral Vaccines for Global Health (2018)
  • Author(s): Kiyono, H.
  • Organizer: CU-UCSD cMAV Symposium 2019, San Diego, USA
  • Invited
• [Presentation] Mucosal Multi-ecological System Creates Novel Strategy for the Prevention and Treatment of Diseases (2018)
  • Author(s): Kiyono, H.
  • Organizer: The 67th Annual Meeting of Japanese Society of Allergology
• [Presentation] The Mucosal Immune System for Symbiosis, Elimination and Vaccine (2018)
  • Author(s): Kiyono, H.
  • Organizer: Japanese Society of Immunology’s Immunology Summer School
• [Presentation] Intestine as a Super Immunological Organ (2018)
  • Author(s): Kiyono, H.
  • Organizer: Intercompany Seminar of Asahi Kogyosha Co., Ltd.
• [Presentation] Equilibrium of Immunity & Symbiosis: From Basic to Vaccine Development (2018)
  • Author(s): Kiyono, H.
  • Organizer: Max Plank Institute for Infection Biology Alumni Meeting
• [Presentation] Mucosal tissue axis for the induction and regulation of immunity, inflammation and symbiosis (2018)
  • Author(s): Kiyono, H.
  • Organizer: Japan-German Immunology Workshop,
• [Presentation] 小腸パイエル板組織内共生細菌アルカリゲネスの免疫機能とアジュバント応用 (2018)
  • Author(s): 柴田納央子、細見晃司、下山敦史、王韻茹、吉井健、深瀬浩一、清野宏、國澤純
  • Organizer: 第15回日本小児消化管感染症研究会
• [Presentation] 共生と排除を司る粘膜マスト細胞の研究/Elucidation of the function of mucosal mast cells for symbiosis and elimination (2018)
  • Author(s): 倉島洋介
  • Organizer: 第22回腸内細菌学会 受賞講演
  • Invited
• [Presentation] 間葉系細胞による免疫末梢教育/Mesenchymal-myeloid cell interactions in renal microenvironment for novel fibrogenic machinery in kidney fibrosis (2018)
  • Author(s): 倉島洋介
  • Organizer: 第42回日本リンパ学会
• [Presentation] Mesenchymal cell-mediated local inflammatory loop in intestinal inflammation (2018)
  • Author(s): Kurashima, Y.
  • Organizer: 2nd Korea-Japan Joint Meeting on Mucosal Immunology
• [Presentation] Bringing mast cells over to our side to overcome allergy” (2018)
  • Author(s): Kurashima, Y.
  • Organizer: 第67回日本アレルギー学会学術大会 シンポジウム18
  • Invited
• [Presentation] 腸管粘膜・皮膚などにおける上皮－間葉－神経系ネットワークによる末梢免疫教育機構 (2018)
  • Author(s): 倉島洋介
  • Organizer: アステラス製薬招待講演
• [Presentation] Synthesis and function of symbiotic bacterial lipopolysaccharide partial structures. (2018)
  • Author(s): Shimoyama, A., Mizote, K., Uto, T., Shibata, N., Lorenzo, F.D., Molinaro, A., Fujimoto, Y., Kunisawa, J., Kiyono, H., Fukase, K.,
  • Organizer: 5th Asian Chemical Biology Conference (Oral)
  • Int'l Joint Research
• [Presentation] Synthesis and Function of Symbiotic Bacterial Lipopolysaccharide Partial Structures, (2018)
  • Author(s): Shimoyama, A., Mizote, K., Uto, T., Shibata, N., Lorenzo F.D., Molinaro, A., Kunisawa, J., Kiyono, H., Fujimoto, Y., Fukase, K.
  • Organizer: Joint Meeting of the Society for Leukocyte Biology (SLB) & the International Endotoxin and Innate Immunity Society(IEIIS
  • Int'l Joint Research
• [Presentation] Synthesis and functions of symbiotic bacterial lipopolysaccharide partial structures. (2018)
  • Author(s): Shimoyama, A., Mizote, K., Uto, T., Lorenzo, F.D., Shibata, N., Fujimoto, Y., Kunisawa, J., Kiyono, K.
  • Organizer: MicrobiotaMi2018 Milano, Italy
• [Presentation] Synthesis and function of symbiotic bacterial lipopolysaccharide partial structures (2018)
  • Author(s): Shimoyama, A., Mizote, K., Uto, T., Shibata, N., Lorenzo, F.D., Molinaro, A., Fujimoto, Y., Kunisawa, J., Kiyono, H., Fukase, K.
  • Organizer: 5th Asian Chemical Biology Conference (Poster)
  • Int'l Joint Research
• [Presentation] Synthesis and immunological function of symbiotic bacterial lipopolysaccharide partial structures. (2018)
  • Author(s): Shimoyama, A., Mizote, K., Uto, T., Lorenzo, F.D., Shibata, N., Fujimoto, Y., Kunisawa, J., Kiyono, H., Molinaro, A. Fukase, K.
  • Organizer: The 14th International Kyoto Conference on New Aspects of Organic Chemistry (IKCOC14)
• [Presentation] CCL28-mediated chemotaxis for the recruitment of IgA-producing plasma cells into the mammary gland depends on the lactation-related but not bacterial stimulus (2018)
  • Author(s): Nochi, T., Niimi, K., Usami, K., Furukawa, M., Sasaki, S., Kiyono, H., Watanabe, K. and Aso, H.
  • Organizer: Mucosal Immunology Course & Symposium (MICS2018)
  • Int'l Joint Research
• [Presentation] 寄生・共生菌由来リポ多糖部分構造の合成と免疫調節機能の解明 (2018)
  • Author(s): 下山敦史、溝手啓介、宇戸智哉、柴田納央子、Flaviana Di Lorenzo、Antonio Molinaro、國澤純、清野宏、藤本ゆかり、深瀬浩一、
  • Organizer: 第37回日本糖質学会年会
• [Presentation] LPS from lymphoid tissue-resident Alcaligenes induces IgA without excessive inflammation via its weak TLR4 agonist activity (2018)
  • Author(s): Shibata, N., Kunisawa, J., Hosomi, K., Fujimoto, Y., Mizote, K., Kitayama, N., Shimoyama, A., Ishii, K.J., Fukase, K. and Kiyono, H.
  • Organizer: 第47回日本免疫学会
• [Presentation] 間葉系細胞による免疫恒常性維持機構 (2018)
  • Author(s): 倉島洋介, 松村成一, 村崎さゆり, 清野宏
  • Organizer: 第8回オルソオルガノジェネシス検討会
• [Presentation] Orally-desensitized mast cells acquired regulatory characteristics for the control of food allergy (2018)
  • Author(s): Kurashima, Y., Takasato, Y., Kiuchi, M., Hirahara, K., Murasaki, S., Kunisawa, J., Kubo, M., Uematsu, S., Nakayama, T., Kiyono, H.
  • Organizer: 第47回日本免疫学会学術集会
• [Book] Mucosal vaccines, Innovation for preventing infectious diseases, Second Edition (2020)
  • Author(s): Kiyono, H., Pascual, D.W.
  • Total Pages: 940
  • Publisher: Elsevier
  • ISBN: 9780128119242
• [Book] Handbook of Immunosenescence: Basic Understanding and Clinical Implications (2019)
  • Author(s): Fujihashi, K., McGhee, J. R., and Kiyono, H.
  • Publisher: Springer Science
• [Book] Lymph Node Metastasis in Gastrointestinal Cancer (2019)
  • Author(s): Nagatake, T., Kunisawa, J., and Kiyono, H.
  • Publisher: Springer
  • ISBN: 9789811046995
• [Book] 免疫生物学（原書第9版）(翻訳) (2019)
  • Author(s): 籠谷領二, 倉島洋介, 清野宏、
  • Publisher: 南江堂
• [Book] SMI textbook of Principles of Mucosal Immunology. 2nd Edition. (2018)
  • Author(s): Kiyono, H., Fujihashi, K., Mestecky, J.
  • Publisher: Garland Science, Taylor & Francis Group, LLC
• [Book] 腎臓内科・泌尿器科7 (2018)
  • Author(s): 山本智久、 倉島洋介、 清野宏
  • Publisher: 科学評論社
• [Book] リンパ学41-2 (2018)
  • Author(s): 切真里奈, 清野宏, 倉島洋介
  • Publisher: 日本リンパ学会
• [Remarks] 地球規模保健課題解決推進のための研究事業（日米医学協力計画）
  • URL: https://www.niaid.nih.gov/research/us-japan-cooperative-medical-science-program-delegation
• [Remarks] SATREPS(地球規模課題対応国際科学技術協力プログラム)
  • URL: https://www.jst.go.jp/global/public/shiryo/brochure2019_J.pdf
• [Remarks] Mucosal Immu., Allergy & Vaccine Development
  • URL: https://medschool.ucsd.edu/som/medicine/divisions/gastro/research/CMAV/Pages/default.aspx
• [Remarks] M Vaccine, Tuberculosis Using Antibody Engineering
  • URL: https://www.ghitfund.org/investment/portfoliodetail/detail/95
• [Patent(Industrial Property Rights)] 肺炎球菌表層タンパク質 (2019)
  • Inventor(s): 幸義和、中橋理佳、清野宏
  • Industrial Property Rights Holder: 幸義和、中橋理佳、清野宏
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019