顎顔面免疫と生殖器免疫のクロストーク

2014 Fiscal Year Annual Research Report

• Project/Area Number: 23229004
• Research Institution: The University of Tokyo
• Principal Investigator: 清野 宏 東京大学, 医科学研究所, 教授 (10271032)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: 性感染症 / 細胞遊走 / HSV2 / ケモカイン / 粘膜免疫 / 経鼻免疫

Outline of Annual Research Achievements

本年度も引き続きHSV2特異的CD4+T細胞の膣粘膜指向性決定分子の同定を試みた。膣粘膜組織型メモリーT細胞を大量調整する事が困難であったため、少数の細胞による次世代シーケンサーによるRNAシークエンス法を用いた解析を行った。経鼻免疫後に膣粘膜に遊走したCD4＋T細胞の発現上昇遺伝子を精査し、遊走関連分子に着目し定量的RT-PCR法および抗体を用いて解析を行った。一連の解析から、最終的に候補分子をCCR1とCCR5に絞り込むことに成功した。これらのケモカイン受容体のシングルノックアウトマウスを用いて、経鼻免疫によって膣の粘膜固有層内に遊走される抗原特異的CD4 T細胞数を比較したところ、CCR5 KOでは野生型に比べ、その数が有意に減少していたが、CCR1 KOでは、若干の減少傾向は示すものの有意な差は認められなかった。これらの二重欠損マウスを作製し、同様の実験を計画したが、CCR1とCCR5をコードする領域は同一染色体に比較的近い位置に存在しているため、二重欠損マウスの作製は原理的に不可能であると考え、断念した。
CCR1とCCR5の共通リガンドとしてCCL3、5が挙げられる。これらのリガンドのいずれか、もしくは全てが上気道・下気道・膣組織において恒常的に産生されているものと予想して、経鼻免疫前後における遺伝子発現を予備実験的に比較した。その結果、予想に反して、特にCCL5が経鼻免疫によって発現が増強されることが示唆された。
また、鼻腔粘膜と膣粘膜における免疫誘導が双方向性を有しているかを検討した。その結果、HSV2を経膣免疫すると、鼻粘膜においても抗原特異的免疫が誘導されていた。従って、CCR1、CCR5を介したCD4＋ T細胞の遊走メカニズムは経鼻免疫、経膣免疫で共通のシステムである事が示唆された。現在CCRIとCCR5を介した鼻腔-生殖器共通リンパ球遊送メカニズムの解明を進めている。

Current Status of Research Progress

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

Reason

詳細を詰める必要はあるものの、本研究の主たる目的である、経鼻免疫によって誘導される抗原特異的免疫担当細胞（CD4＋ T細胞）の膣粘膜組織指向性を決定する分子機構が、CCR1、5－CCL3、4，5であることを強く示唆するデータを得ることができたため。

Strategy for Future Research Activity

HSV2-CD4＋ T細胞の膣粘膜指向性決定分子として、CCR1とCCR5に候補を絞ったが、これらの受容体が重複的に働いているかどうかを明らかにするためには、これらの受容体の二重欠損マウスを作成し、比較検討する必要がある。しかし、概要で述べたようにこのマウスの作製は現実的に不可能である。その代替手段として、CCR5欠損マウスに抗CCR1抗体を投与することで機能的な二重欠損マウスを用意し比較検討する。また、これらの受容体の共通リガンドとしてCCL3, 5が挙げられるが、これらに対するブロッキング抗体の投与を行うことで、実際に抗原特異的CD4＋ T細胞の遠隔遊走に関わるリガンドの同定も行う。
CCR1とCCR5の共通リガンドとしてCCL3、5が挙げられるが、特にCCL5に関しては経鼻免疫によりその遺伝子発現量が顕著に上昇していた。この結果は、膣粘膜上皮細胞や間質系細胞からの産生に加えて、膣組織に遊走してきた免疫担当細胞がこれらのリガンドをさらに産生していることを意味している。この現象が、ポジティブフィードバックであり、さらなる抗原特異的CD4＋ T細胞の遊走を促しているのか、もしくは、膣粘膜上皮細胞や間質系細胞からこれらのリガンドは産生されておらず、CD4＋ T細胞に先んじて何らかのメカニズムで膣組織に遊走しうる他の免疫細胞によって産生されているものなのかは現在のところ不明であり、最終年度である次年度では明らかにすべき点である。そこで、経鼻免疫後の膣組織におけるリガンド産生量のKineticsを細かく観察し、抗原特異的CD4＋ T細胞の遊走のKineticsと比較する予定である。

Research Products

• [Journal Article] Mucosal immunosenescence in the gastrointestinal tract: A mini-review. (2015)
  • Author(s): Sato, S., Kiyono, H. and Fujihashi, K.
  • Journal Title: Gerontology Volume: - Pages: in press
  • DOI: DOI:10.1159/000368897
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Loss of lymph node fibroblastic reticular cells and high endothelial cells is associated with humoral immunodeficiency in mouse graft-versus-host disease. (2015)
  • Author(s): Suenaga, F., Ueha, S., Abe, J., Kosugi-Kanaya, M., Wang, Y., Yokoyama, A., Shono, Y., Shand, F. H., Morishita, Y., Kunisawa, J., Sato, S., Kiyono, H. and Matsushima, K.
  • Journal Title: J. Immunol. Volume: 194(1) Pages: 398-406
  • DOI: doi: 10.4049/jimmunol.1401022.
  • Peer Reviewed / Open Access
• [Journal Article] The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells. (2015)
  • Author(s): Tsai, S-H., Kinoshita, M., Kusu, T., Kayama, H., Okumura, R., Ikeda, K., Shimada, Y., Takeda, A., Yoshikawa, S., Obata-Ninomiya, K., Kurashima, Y., Sato, S., Umemoto, E., Kiyono, H., Karasuyama, H. and Takeda, K.
  • Journal Title: Immunity Volume: 42(2) Pages: 279-293
  • DOI: doi: 10.1016/j.immuni.2015.01.015.
  • Peer Reviewed / Open Access
• [Journal Article] Determination of genomic location and structure of the transgenes in marker-free rice-based cholera vaccine by using whole genome resequencing approach. (2015)
  • Author(s): Mejima, M., Kashima, K., Kuroda, M., Takeyama, N., Kurokawa S., Fukuyama Y., Kiyono H., Itoh, K., Mitsui, T., and Yuki, Y.
  • Journal Title: Plant Cell Tiss. Organ Cult. Volume: 120 Pages: 35-48
  • DOI: doi: 10.1007/s11240-014-0575-4
  • Peer Reviewed
• [Journal Article] Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques. (2015)
  • Author(s): Fukuyama, Y., Yuki, Y., Katakai, Y., Harada, N., Takahashi, H., Takeda, S., Mejima, M., Joo, S., Kurokawa, S., Sawada, S., Shibata, H., Park, EJ., Fujihashi., K, Briles, D., Yasutomi, Y., Tsukada, H., Akiyoshi, K., Kiyono, H.
  • Journal Title: Mucosal Immunol. Volume: - Pages: in press
  • DOI: doi: 10.1038/mi.2015.5.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel transgenic rice-based vaccines. (2015)
  • Author(s): Azegami, T., Itoh, H., Kiyono, H. and Yuki, Y.
  • Journal Title: Arch. Immunol. Ther. Exp. Volume: 63(2) Pages: 87-99
  • DOI: doi: 10.1007/s00005-014-0303-0.
  • Peer Reviewed / Open Access
• [Journal Article] Comparative whole-genome analyses of selection marker‐free rice-based cholera toxin B-subunit vaccine lines and wild-type lines. (2015)
  • Author(s): Kashima, K., Mejima, M., Kurokawa, S., Kuroda, M., Kiyono, H. and Yuki, Y.
  • Journal Title: BMC Genomics Volume: 48 Pages: 16(1)
  • DOI: doi:10.1186/s12864-015-1285-y
  • Peer Reviewed / Open Access
• [Journal Article] Vitamins mediate immunological homeostasis and diseases at the surface of the body. (2015)
  • Author(s): Kunisawa J. and Kiyono H.
  • Journal Title: Endocr. Metab. Immune Disord. Drug Targets Volume: 15(1) Pages: 25-30
  • DOI: doi: 10.2174/1871530314666141021114651
  • Peer Reviewed
• [Journal Article] Negative regulation of DSS-induced experimental colitis by PILRα. (2015)
  • Author(s): Kishida, K., Kohyama, M., Kurashima, Y., Kogure, Y., Wang, J., Hirayasu, K., Suenaga, T., Kiyono, H., Kunisawa, J. and Arase, H.
  • Journal Title: Int. Immunol. Volume: - Pages: in press
  • DOI: doi: 10.1093/intimm/dxv004
  • Peer Reviewed / Open Access
• [Journal Article] レチノイン酸代謝による皮膚バリアの恒常性維持－線維芽細胞によるマスト細胞調節機構－ (2015)
  • Author(s): 佐藤健、倉島洋介、國澤純、清野宏
  • Journal Title: 臨床免疫・アレルギー科 Volume: 63(2) Pages: 139-145
• [Journal Article] 腸管バリアとしての糖鎖修飾とその制御 (2015)
  • Author(s): 後藤義幸、清野宏
  • Journal Title: 実験医学 Volume: 33(4) Pages: 544-549
• [Journal Article] Vaginal memory T cells induced by intranasal vaccination are critical for protective T cell recruitment and prevention of genital HSV-2 disease. (2014)
  • Author(s): Sato, A., Suwanto, A., Okabe, M., Sato, S., Nochi, T., Imai, T., Koyanagi, N., Kunisawa, J., Kawaguchi, Y. and Kiyono, H.
  • Journal Title: J Virol. Volume: 88(23) Pages: 13699-13708
  • DOI: doi: 10.1128/JVI.02279-14.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mucosal adjuvants for vaccines to control upper respiratory infections in the elderly. (2014)
  • Author(s): Fujihashi, K., Sato S., and Kiyono, H.
  • Journal Title: Exp. Gerontol. Volume: 54 Pages: 21-26
  • DOI: doi: 10.1016/j.exger.2014.01.006.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Innate lymphoid cells regulate intestinal epithelial cell glycosylation. (2014)
  • Author(s): Goto, Y., Obata, T., Kunisawa, J., Sato, S., Ivanov, I., Lamichhane, A., Takeyama, N., Kamioka, M., Sakamoto, M., Matsuki, T., Setoyama, H., Imaoka, A., Uematsu, S., Akira, S., Domino, S., Kulig, P., Becher, B., Renauld, J-C., Sasakawa, C., Umesaki, Y., Benno, Y. and Kiyono, H.
  • Journal Title: Science Volume: 345(6202) Pages: 1254009
  • DOI: doi: 10.1126 /science.1254009.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The enzyme cyp26B1 mediates inhibition of mast cell activation by fibroblasts to maintain skin-barrier homeostasis. (2014)
  • Author(s): Kurashima, Y., Amiya, T., Fujisawa, K., Shibata, N., Suzuki, Y., Kogure. Y., Hashimoto, E., Otsuka, A., Kabashima, K., Sato, S., Sato, T., Kubo, M., Akira, S., Miyake, K., Kunisawa, J., and Kiyono, H.
  • Journal Title: Immunity Volume: 40 Pages: 530-541
  • DOI: doi: 10.1016/j.immuni.2014.01.014.
  • Peer Reviewed / Open Access
• [Journal Article] Challenge in mucosal vaccines for the control of infectious diseases. (2014)
  • Author(s): Azegami, T., Yuki, Y., and Kiyono, H.
  • Journal Title: Int. Immunol. Volume: 26 Pages: 517-528
  • DOI: doi: 10.1093/intimm/dxu063.
  • Peer Reviewed / Open Access
• [Journal Article] The mucosal immune system for vaccine development. (2014)
  • Author(s): Lamichhane, A., Azegami, T. and Kiyono, H.
  • Journal Title: Vaccine Volume: 32(49) Pages: 6711-6723
  • DOI: doi: 10.1016/j.vaccine.2014.08.089.
  • Peer Reviewed / Open Access
• [Journal Article] New era for mucosal mast cells: their roles in inflammation, allergic immune responses and adjuvant development. (2014)
  • Author(s): Kurashima, Y. and Kiyono, H.
  • Journal Title: Exp. Mol. Med. Volume: 46 Pages: e83
  • DOI: doi: 10.1038/emm.2014.7.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Peyer's patches and mesenteric lymph nodes cooperatively promote enteropathy in a mouse model of food allergy. (2014)
  • Author(s): Nakajima-Adachi, H., Kikuchi, A., Fujimura, Y., Shibahara, K., Makino, T., Goseki-Sone, M., Kihara-Fujioka, M., Nochi, T., Kurashima, Y., Igarashi, O., Yamamoto, M., Kunisawa, J., Toda, M., Kaminogawa, S., Sato, R., Kiyono, H., and Hachimura, S.
  • Journal Title: PLoS One. Volume: 9 Pages: e107492
  • DOI: doi: 10.1371/journal.pone.0108294.
  • Peer Reviewed / Open Access
• [Journal Article] Specific expression of apolipoprotein A-IV in the follicle-associated epithelium of the small intestine. (2014)
  • Author(s): Tokuhara, D., Nochi, T., Matsumura, A., Mejima, M., Takahashi, Y., Kurokawa, S., Kiyono, H. and Yuki Y.
  • Journal Title: Dig. Dis. Sci. Volume: 59 Pages: 2682-2692
  • DOI: doi: 10.1007/s10620-014-3203-6.
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of intestinal IgA responses by dietary palmitic acid and its metabolism. (2014)
  • Author(s): Kunisawa, J., Hashimoto, E., Inoue, A., Nagasawa R., Suzuki, Y., Ishikawa, I., Shikata, S., Arita, M., Aoki, J. and Kiyono, H.
  • Journal Title: J. Immunol. Volume: 193 Pages: 1666-1671
  • DOI: doi: 10.4049/jimmunol.1302944.
  • Peer Reviewed / Open Access
• [Journal Article] Runx2-I isoform contributes to fetal bone formation even in the absence of specific N-terminal amino acids. (2014)
  • Author(s): Okura, H., Sato, S., Kishikawa, S., Kaneto, S., Nakashima, T., Yoshida, N., Takayanagi, H. and Kiyono, H.
  • Journal Title: PLoS One. Volume: 9(9) Pages: e108294
  • DOI: doi:10.1371/journal.pone.0108294
  • Peer Reviewed / Open Access
• [Journal Article] Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice. (2014)
  • Author(s): Hiyama, S., Iijima, H., Shinzaki, S., Inoue, T., Shiraishi, E., Kawai, S., Araki, M., Kato, M., Hayashi, Y., Nishida, T., Fujii, H., Mukai, A., Shibata, N., Sato, S., Kiyono, H., Gotoh, K., Motooka, D., Nakamura, S., Iida, T., Tsujii, M., and Takehara, T.
  • Journal Title: Inflamm Bowel Dis. Volume: 20 Pages: 790-799
  • DOI: 10.1097/MIB.0000000000000017
  • Peer Reviewed
• [Journal Article] Generation of colonic IgA-secreting cells in the cecal patch. (2014)
  • Author(s): Masahata, K., Umemoto, E., Kayama, Kiyono, H., Fagarasan, S., Iida, T., Ishii, M., and Takeda, K.
  • Journal Title: Nat Commun. Volume: 5 Pages: 3704
  • DOI: doi: 10.1038/ncomms4704.
  • Peer Reviewed / Open Access
• [Journal Article] A rice-based soluble form of a murine TNF -specific llama variable domain of heavy-chain antibody suppresses collagen -induced arthritis in mice. (2014)
  • Author(s): Abe, M., Yuki, Y., Kurokawa, S., Mejima, M., Kuroda, M., Park, E.J., Scheller, J. Nakanishi, U. and Kiyono, H.
  • Journal Title: J. Biotechnol. Volume: 10:175 Pages: 45-52
  • DOI: doi: 10.1016/j.jbiotec.2014.02.005.
  • Peer Reviewed / Open Access
• [Journal Article] 粘膜ワクチンを基盤とした次世代ワクチンの開発 (2014)
  • Author(s): 福山賀子、清野宏
  • Journal Title: 最新医学 Volume: 69(4) Pages: 62-69
• [Journal Article] 次世代ワクチン開発への課題と挑戦-経口ワクチン- (2014)
  • Author(s): 鹿島光司、幸義和、清野宏
  • Journal Title: BIO INDUSTRY Volume: 31(6) Pages: 4-10
• [Journal Article] 抑制型免疫システムを応用した次世代型抗アレルギーワクチンの開発 (2014)
  • Author(s): 高里良宏、倉島洋介、清野宏、國澤純
  • Journal Title: BIO INDUSTRY Volume: 31(6) Pages: 55-60
• [Journal Article] 自然リンパ球による腸管上皮細胞の糖鎖修飾誘導・制御システム (2014)
  • Author(s): 後藤義幸、清野宏
  • Journal Title: 分子消化器病 Volume: 11(4) Pages: 86-88
• [Journal Article] 細胞外核酸を介したマスト細胞の活性化と炎症性腸疾患 (2014)
  • Author(s): 倉島洋介、清野宏、國澤純
  • Journal Title: 生化学 Volume: 86(6) Pages: 798-802
• [Presentation] “Mucosal Innate Lymphoid Cells and Mast Cells for the Regulation of Symbiosis and Inflammation” (2015)
  • Author(s): Kiyono, H.
  • Organizer: World Immune Regulation Meeting IX
  • Place of Presentation: Davos, Switzerland.
  • Year and Date: 2015-03-21
  • Invited
• [Presentation] “Innovative Oral Vaccine：MucoRice” (2015)
  • Author(s): Kiyono, H.
  • Organizer: “2015 Seminar for the Quality and Safety Improvements of Dental Practice” Kanagawa Dental Association
  • Place of Presentation: Kanagawa, Japan.
  • Year and Date: 2015-03-08
  • Invited
• [Presentation] “The Mucosal Immune System for Symbiosis and Elimination” (2015)
  • Author(s): Kiyono, H.
  • Organizer: The 34th Shirokane Symposium, The 50th Anniversary of Founding of the Kitasato University School of pharmacy
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2015-02-28
  • Invited
• [Presentation] “Mucosal Immunity: The Adaptation of oral-Digestive Immune System for Vaccine Development” (2015)
  • Author(s): Kiyono, H.
  • Organizer: The 3rd Medical Advisor Workshop, The Academy of Clinical Dentistry
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2015-02-11
  • Invited
• [Presentation] Gut Microflora Influences Pathology in the Kawasaki Disease (KD) VasculitisMouse Model (2015)
  • Author(s): Wakita, D., Kurashima, Y., Takasato, Y., Lee, Y., Shimada, K., Chen, S., Crother, T. R., Fishbein, M. C., Lehman, T.J.A., Kiyono, H., and Arditi , M.
  • Organizer: International Kawasaki Disease Symposium
  • Place of Presentation: Hawaii, USA.
  • Year and Date: 2015-02-03 – 2015-02-06
• [Presentation] “Advancing the Knowledge of Immunology for Disease Treatments.” (2015)
  • Author(s): Kiyono, H.
  • Organizer: Science Council of Japan and The Pharmaceutical Society of Japan Symposium
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2015-01-09
  • Invited
• [Presentation] Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation. (2014)
  • Author(s): Goto, Y., Panea, C., Lee, C. and Ivanov, I.
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Kyoto, Japan.
  • Year and Date: 2014-12-12
• [Presentation] E-NPP3 (CD203c) negatively regulates ATP-dependent allergic responses by basophils and mast cells. (2014)
  • Author(s): Tsai, S-H., Kinoshita, M., Kayama, H., Okuma, R., Kiyono, H., Karasuyama, H. and Takeda, K.
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Kyoto, Japan.
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Loss of lymph node fibroblastic reticular cells and high endothelial cells underlies humoral immunodeficiency in mouse GVHD. (2014)
  • Author(s): Ueha, S., Suenaga, F., Abe, J., Kosugi, M., Shono, Y., Kunisawa, J., Sato S., Kiyono, H. and Matsushima, K.
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Kyoto, Japan.
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Resistance to helminthic infection is dependent on mast cell activation mediated by ATP in Spi-B-deficient mice. (2014)
  • Author(s): Shimokawa, C., Kanaya, T., Ishikawa, K., Kurashima Y., Kiyono, H., Kaisho T. and Ohno, H.
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology, Kyoto
  • Place of Presentation: Kyoto, Japan.
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Critical role of TSLP-TSLPR interaction in inducing secretory IgA responses after mucosal immunizations. (2014)
  • Author(s): Joo, S., Fukuyama, Y., Yuki Y., Kurashima, Y., Ziegler, S.F., Park E-J. and Kiyono, H.
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Kyoto, Japan.
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Vaginal resident memory T cells induced by intranasal vaccination are critical for early clearance of genital HSV-2 infection. (2014)
  • Author(s): Suwanto, A., Sato A., Sato S., Nochi, T., Kunisawa, J. and Kiyono, H.
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] “Rice Protein Body and Cationic Nanogel as Antigen Delivery Vehicle for Mucosal Vaccines” (2014)
  • Author(s): Kiyono, H.
  • Organizer: 8th International Symposium on Nanomedicine (ISNM2014)
  • Place of Presentation: Matsuyama, Ehime.
  • Year and Date: 2014-12-06
  • Invited
• [Presentation] “Microbial Molding of Mucosal Immunity” (2014)
  • Author(s): Kiyono, H.
  • Organizer: ACR/ARHP Annual Meeting
  • Place of Presentation: Boston, USA.
  • Year and Date: 2014-11-14
  • Invited
• [Presentation] “Rice-based Oral Vaccine “MucoRice” for the Control of Enteric Diarrheal Disease” (2014)
  • Author(s): Kiyono, H.
  • Organizer: The 62nd Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2014-11-10
  • Invited
• [Presentation] “Cross-talk between the Mucosal Immune System and Environmental Factors” (2014)
  • Author(s): Kiyono, H.
  • Organizer: 11th Nestlé International Nutrition Symposium on “Nutrition and the Human Gut Microbiome”
  • Place of Presentation: Lausanne, Switzerland.
  • Year and Date: 2014-10-23
  • Invited
• [Presentation] “Mucosal Innate Immune System and Vaccine Development” (2014)
  • Author(s): Kiyono, H.
  • Organizer: The 1st International Symposium on Mucosal Immunity and Vaccine Development 2014.
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2014-10-21
  • Invited
• [Presentation] “Tissue-specific signals control mast cell function for the maintenance of tissue homeostasis” (2014)
  • Author(s): Kurashima, Y.
  • Organizer: The 1st International Symposium on Mucosal Immunity and Vaccine Development 2014.
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2014-10-21
  • Invited
• [Presentation] "Mucosal Connections Between Airway and Reproductive Immunity" (2014)
  • Author(s): Kiyono, H.
  • Organizer: 10th Research Symposium on Human Natural Defense System in Conjunction with PRAMS 2014 in Commemoration of the 10th Anniversary of The Airway Mucus Institute
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] Tissue-specific signals control mast cell function for the maintenance of tissue homeostasis (2014)
  • Author(s): Kurashima, Y.
  • Organizer: 2nd Novo Nordisk Innovation Summit 2014
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2014-10-02
  • Invited
• [Presentation] “Mucosal Links between Innate-epithelial Cells and Commensal Flora for the Development of New Immune-prevention and -therapy” (2014)
  • Author(s): Kiyono, H.
  • Organizer: 2nd Novo Nordisk Innovation Summit 2014
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2014-10-01
  • Invited
• [Presentation] “Development of Next Generation Vaccine based on Mucosal Immunology~Future of Mucosal Vaccine” (2014)
  • Author(s): Kiyono, H.
  • Organizer: The 65th Kanto Region Otorhinolaryngology Allergy Discussion Group
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2014-09-21
  • Invited
• [Presentation] “Innate Lymphoid Cells Regulate Intestinal Epithelial Cell Fucosylation for Symbiosis and Elimination” (2014)
  • Author(s): Kiyono, H.
  • Organizer: The 26th Symposium on Microbial Sciences ~The Symphony of Microbial Science and Medical care~
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2014-09-19
  • Invited
• [Presentation] “Trends in Immunological Memory and Vaccine Development”, Organizer and Speaker, “Mucosal Immunity and Vaccine Development” (2014)
  • Author(s): Kiyono, H.
  • Organizer: The 2nd Symposium of International Immunological Memory and Vaccine Forum, (IIMVF)
  • Place of Presentation: La Jolla, USA.
  • Year and Date: 2014-08-26
  • Invited
• [Presentation] Whole genome analysis of selection marker-free MucoRice-CTB, a rice-based oral cholera vaccine (2014)
  • Author(s): Kashima, K.
  • Organizer: International Plant Biotechnology Association
  • Place of Presentation: Melbourne, Australia.
  • Year and Date: 2014-08-10 – 2014-08-15
• [Presentation] “Oral Vaccine, MucoRice Fighting against the Diarrhea” (2014)
  • Author(s): Kiyono, H.
  • Organizer: JSI organized Public Lecture Series Meneki Fushigi Mirai 2014.
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2014-08-10
  • Invited
• [Presentation] “Reciprocal Cooperation of Intra-tissue Commensal Bacteria, Innate Lymphoid Cells and Mast Cells for the Integrated Mucosal Immunoregulation” (2014)
  • Author(s): Kiyono, H.
  • Organizer: The 38th Aso Symposium 2014.
  • Place of Presentation: Kumamoto, Japan.
  • Year and Date: 2014-07-25 – 2014-07-26
  • Invited
• [Presentation] “Development of Mucosal Immunology Driven Rice-based Vaccine “MucoRice” by the Fusion Research of Medical, Agricultural and Engineering Sciences” (2014)
  • Author(s): Kiyono, H.
  • Organizer: The 13th Shikoku Immunology Forum 2014
  • Place of Presentation: Tokushima, Japan.
  • Year and Date: 2014-06-21
  • Invited
• [Presentation] “Mucosal Connections between Microbial Ecology and Immunity for the Homeostasis and Inflammatory Responses” (2014)
  • Author(s): Kiyono, H.
  • Organizer: 7th International Immunonutrition Workshop -Eating for Preventing-
  • Place of Presentation: Carovigno, Italy.
  • Year and Date: 2014-05-01
  • Invited
• [Presentation] ”Fusion of Medical, Plant and Engineering Science Led to the Creation of Rice-based Vaccine, MucoRice” (2014)
  • Author(s): Kiyono, H.
  • Organizer: SKIL Future Forum -Science Leads to Safe Life-
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2014-04-18
  • Invited
• [Presentation] “Can We Prevent Infectious Diseases by Rice?” (2014)
  • Author(s): Kiyono, H.
  • Organizer: Seminar for Knowledge of Hub, National University Joint Usage-Research Center
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2014-04-18
  • Invited
• [Remarks] 東京大学医科学研究所炎症免疫学分野 業績
  • URL: http://www.ims.u-tokyo.ac.jp/enmen/science/s_2014jp.html