Clarification of the intestinal immune regulatory mechanisms by dendritic cells

• Project/Area Number: 26293106
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Wakayama Medical University
• Principal Investigator: Tsuneyasu Kaisho 和歌山県立医科大学, 先端医学研究所, 教授 (60224325)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 樹状細胞 / 腸管免疫 / ケモカイン / 免疫応答 / T細胞 / 遺伝子改変マウス / サブセット / ケモカイン受容体 / クロスプレゼンテーション / XCR1

Outline of Final Research Achievements

We have generated the mutant mice lacking a dendritic cell subset expressing a chemokine receptor, XCR1, (XCR1+DC) constitutively and have found that XCR1+DC was required for keeping intestinal immune homeostasis. This indicates novel XCR1+DC-dependent mechanisms for intestinal immune regulation. We have also generated the mutant mice expressing a fluorescence protein, Kikume, in XCR1+DC. By analyzing the mice, we have achieved in visualizing functional behavior and interaction of XCR1+DC with T cells.

Research Products

• [Int'l Joint Research] Singapore Immunology Network (SIgN)(シンガポール)
• [Int'l Joint Research] University of Bonn/University Hospital Cologne/University of Muenchen(ドイツ)
• [Int'l Joint Research] Harvard Medicl School/Aduro Biotech/Mainz University(米国)
• [Int'l Joint Research] The Australian National University/Telethon Kids Institute(オーストラリア)
• [Int'l Joint Research] ICGEB(イタリア)
• [Int'l Joint Research]
• [Int'l Joint Research] Singapore Immunology Network (SIgN)(シンガポール)
• [Int'l Joint Research] Malaghan Institute of Medical Research(ニュージーランド)
• [Int'l Joint Research] University of Bonn(ドイツ)
• [Journal Article] In vivo ablation of dendritic cell subset expressing the chemokine receptor XCR1. (2016)
  • Author(s): H. Hemmi, K. Hoshino, T. Kaisho.
  • Journal Title: Methods Mol Biol. Volume: 1423 Pages: 247-53
  • DOI: 10.1007/978-1-4939-3606-9_17
  • ISBN: 9781493936045, 9781493936069
  • Peer Reviewed
• [Journal Article] Critical role for CD103+/CD141+ dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in melanoma. (2016)
  • Author(s): E. W. Roberts, M. L. Broz, M. Binnewies, M. B. Headley, A. E. Nelson, D. M. Wolf, T. Kaisho, D. Bogunovic, N. Bhardwaj, M. F. Krummel.
  • Journal Title: Cancer Cell Volume: 30 Issue: 2 Pages: 324-336
  • DOI: 10.1016/j.ccell.2016.06.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney (2016)
  • Author(s): Sato Y, Mii A, Hamazaki Y, Fujita H, Nakata H, Masuda K, Nishiyama S, Shibuya S, Haga H, Ogawa O, Shimizu A, Narumiya S, Kaisho T, Arita M, Yanagisawa M, Miyasaka M, Sharma K, Minato N, Kawamoto H, and Yanagita M.
  • Journal Title: JCI. Insight. Volume: 1 Issue: 11
  • DOI: 10.1172/jci.insight.87680
  • NAID: 120005820865
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Antigen-specific cytotoxic T lymphocytes target airway CD103(+) and CD11b(+) dendritic cells to suppress allergic inflammation (2016)
  • Author(s): Daniels N. J., Hyde E., Ghosh S., Seo K., Price K. M., Hoshino K., Kaisho T., Okada T. and Ronchese F.
  • Journal Title: Mucosal immunology Volume: 9 Issue: 1 Pages: 229-239
  • DOI: 10.1038/mi.2015.55
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node (2016)
  • Author(s): Kitano M., Yamazaki C., Takumi A., Ikeno T., Hemmi H., Takahashi N., Shimizu K., Fraser S. E., Hoshino K., Kaisho T. and Okada T.
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 113 Issue: 4 Pages: 1044-1049
  • DOI: 10.1073/pnas.1513607113
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis. (2016)
  • Author(s): Ohta T, Sugiyama M, Hemmi H, Yamazaki C, Okura S, Sasaki I, Fukuda Y, Orimo T, Ishii KJ, Hoshino K, Ginhoux F, Kaisho T.
  • Journal Title: Scientific Reports Volume: 162 Issue: 1 Pages: 23505-23505
  • DOI: 10.1038/srep23505
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Robust anti-viral immunity requires multiple distinct t cell-dendritic cell interactions. (2015)
  • Author(s): S. Eickhoff, A. Brewitz, M. Y. Gerner, F. Klauschen, K. Komander, H. Hemmi, N. Garbi, T. Kaisho, R. N. Germain, W. Kastenmüller.
  • Journal Title: Cell Volume: 162 Issue: 6 Pages: 1322-1337
  • DOI: 10.1016/j.cell.2015.08.004
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] PDLIM1 inhibits NF-κB-mediated inflammatory signaling by sequestering the p65 subunit of NF-κB in the cytoplasm. (2015)
  • Author(s): Ono, R., Kaisho, T., Tanaka, T.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 18327-18327
  • DOI: 10.1038/srep18327
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 自己免疫疾患における自然免疫システムの役割 (2015)
  • Author(s): 改正恒康
  • Journal Title: 実験医学（増刊） Volume: 33 Pages: 1871-76
• [Journal Article] 樹状細胞サブセットと内因性リガンド (2015)
  • Author(s): 大田友和、改正恒康
  • Journal Title: 炎症と免疫 Volume: 23 Pages: 477-482
• [Journal Article] Transcription factor IRF8 plays a critical role in the development of murine basophils and mast cells. (2015)
  • Author(s): H. Sasaki, D. Kurotaki, N. Osato, H. Sato, I. Sasaki, S. Koizumi, H. Wang, C. Kaneda, A. Nishiyama, T. Kaisho, H. Aburatani, H. C. Morse III, K. Ozato, T. Tamura.
  • Journal Title: Blood Volume: 125(2) Issue: 2 Pages: 358-369
  • DOI: 10.1182/blood-2014-02-557983
  • Peer Reviewed / Open Access
• [Journal Article] Transcriptional Control of dendritic cell differentiation. (2014)
  • Author(s): I. Sasaki, T. Kaisho
  • Journal Title: Curr. Top. Microbiol. Immunol. Volume: 381 Pages: 257-278
  • DOI: 10.1007/82_2014_378
  • ISBN: 9783319073941, 9783319073958
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Homeostatic inflammation in innate immunity. (2014)
  • Author(s): K. Miyake, T. Kaisho
  • Journal Title: Curr.Opin. Immunol. Volume: 30 Pages: 85-90
  • DOI: 10.1016/j.coi.2014.08.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Olfactory plays a key role in spatiotemporal pathogenesis of cerebral malaria. (2014)
  • Author(s): H. Zhao, T. Aoshi, S. Kawai, Y. Mori, A. Konishi, M. Ozkan, Y. Fujita, Y. Haseda, M. Shimizu, M. Kohyama, K. Kobiyama, K. Eto, J. Nabekura, T. Horii, T. Ishino, M. Yuda, H. Hemmi, T. Kaisho, S. Akira, M. Kinoshita, K. Tohyama, Y. Yoshioka, K. J. Ishii, C. Coban
  • Journal Title: Cell Host Microbe Volume: 15 Issue: 5 Pages: 551-563
  • DOI: 10.1016/j.chom.2014.04.008
  • Peer Reviewed / Open Access
• [Journal Article] Single-Cell Imaging of Caspase-1 Dynamics Reveals an All-or-None Inflammasome Signaling Response. (2014)
  • Author(s): Liu, T., Yamaguchi, Y., Shirasaki, Y., Shikada, K., Yamagishi, M., Hoshino, K., Kaisho, T., Takemoto, K., Suzuki, T., Kuranaga, E., Ohara, O., Miura, M.
  • Journal Title: Cell Reports Volume: 8 Issue: 4 Pages: 974-982
  • DOI: 10.1016/j.celrep.2014.07.012
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] IL-27 affects helper T cell responses via regulation of PGE2 production by macrophages. (2014)
  • Author(s): Y. Sato, H. Hara, T. Okuno, N. Ozaki, S. Suzuki, T. Yokomizo, T. Kaisho, H. Yoshida.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 451 Issue: 2 Pages: 215-221
  • DOI: 10.1016/j.bbrc.2014.07.096
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Homeostasis of thymus-derived Foxp3+ regulatory T cells is controlled by ultraviolet B exposure in the skin. (2014)
  • Author(s): S. Yamazaki, A. Nishioka, S. Kasuya, N. Ohkura, H. Hemmi, T. Kaisho, O. Taguchi, S. Sakaguchi, A. Morita
  • Journal Title: J Immunol Volume: 193(11) Issue: 11 Pages: 5488-97
  • DOI: 10.4049/jimmunol.1400985
  • Peer Reviewed
• [Journal Article] Limitation of immune tolerance-inducing thymic epithelial cell development by Spi-B-mediated negative feedback regulation. (2014)
  • Author(s): N. Akiyama, M. Shinzawa, M. Miyauchi, H. Yanai, R. Tateishi, Y. Shimo, D. Ohshima, K. Matsuo, I. Sasaki, K.Hoshino, G. Wu, S. Yagi, J. Inoue, T. Kaisho, T. Akiyama
  • Journal Title: J. Exp. Med Volume: 211 Issue: 5 Pages: 2425-2438
  • DOI: 10.1084/jem.20140825
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] HSP70 mediates degradation of the p65 subunit of nuclear factor κB to inhibit inflammatory signaling (2014)
  • Author(s): T. Tanaka, A. Shibazaki, R. Ono, T. Kaisho
  • Journal Title: Sci. Signal Volume: 7(356) Issue: 356
  • DOI: 10.1126/scisignal.2005533
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 治療抵抗性EBウイルス関連血球貪食症候群を発症したX連鎖性知的障害例における新規CCDC22遺伝子変異の同定 (2017)
  • Author(s): 山下友佑, 田村志宣, 岩橋吉史, 佐々木泉, 西川彰則, 金澤伸雄, 邊見弘明, 村田晋一, 改正恒康, 大島孝一, 今留謙一, 吉浦孝一郎, 園木孝志.
  • Organizer: 第10回日本免疫不全症研究会
  • Place of Presentation: 東京（千代田）
• [Presentation] Intestinal M cells contribute to maintenance of gut immune homeostasis. (2016)
  • Author(s): Y. Nakamura, C. Yarimizu, T. Kaisho, J. Kunisawa, H. Kiyono, K. Hase.
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄（宜野湾）
  • Year and Date: 2016-12-05
• [Presentation] Crosstalk between XCR1-expressing dendritic cells and intenstinal T cells keeps intenstinal homeostasis through the XCR1-XCL1 chemokine axis. (2016)
  • Author(s): T. Ohta, H. Hemmi, Y. Fukuda, I. Sasaki, T. Orimo, T. Kaisho.
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄（宜野湾）
  • Year and Date: 2016-12-05
• [Presentation] Metabolic basis for cholera toxin-induced IL-1beta production in synergy with lipopolysaccharides. (2016)
  • Author(s): I. Sasaki, S. Fukuda, T. Orimo, H. Hemmi, Y. Fukuda, T. Ohta, T. Kaisho.
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄（宜野湾）
  • Year and Date: 2016-12-05
• [Presentation] Dose Juzen-Taiho-To have immuno-suppressive effect? (2016)
  • Author(s): K. Kanno, M. Odanaka, M. Imai, A. Nishioka, M. Nose, H. Hemmi, T. Kaisho, A. Morita, S. Yamazaki.
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄（宜野湾）
  • Year and Date: 2016-12-05
• [Presentation] Spi-B plays a protective role in pressure overload-induced heart failure through attenuation of cardiac inflammation. (2016)
  • Author(s): A. Kimura, Y. Ishida, M. Nosaka, Y. Kuninaka, I. Sasaki, Y. Fukuda, T. Kaisho, T. Kondo.
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄（宜野湾）
  • Year and Date: 2016-12-05
• [Presentation] Chemokine-directed cancer antigen peptide delivery to the XCR1+ dendritic cell subset. (2016)
  • Author(s): Y. Mizumoto, H. Hemmi, M. Katsuda, M. Sugiyama, T. Ohta, Y. Fukuda, A. Miyamoto, H. Yamaue T. Kaisho.
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄（宜野湾）
  • Year and Date: 2016-12-05
• [Presentation] The absence of Spi-B exaggerates acute aortic dissection in mice. (2016)
  • Author(s): A. Taruya, A. Kimura, M. Nosaka, Y. Ishida, Y. Kuninaka, I. Sasaki, Y. Fukuda, T. Kaisho, T. Kondo.
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄（宜野湾）
  • Year and Date: 2016-12-05
• [Presentation] XCR1+樹状細胞をターゲットとした新規がんペプチドワクチン療法の開発 (2016)
  • Author(s): 水本有紀、勝田将裕、宮澤基樹、北畑裕司、宮本篤、中森幹人、尾島敏康、早田啓治、北谷純也、邊見弘明、改正恒康、山上裕機
  • Organizer: 第29回日本バイオセラピィ学会学術集会総会
  • Place of Presentation: 福岡（久留米）
  • Year and Date: 2016-12-01
• [Presentation] Development of new cancer peptide vaccine therapy that targets XCR1+ dendritic cell (2016)
  • Author(s): 水本有紀、勝田将裕、宮澤基樹、北畑裕司、津村亜矢子、宮本篤、中森幹人、尾島敏康、邊見弘明、改正恒康、山上裕機
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 神奈川（横浜）
  • Year and Date: 2016-10-06
• [Presentation] XCR1＋樹状細胞をターゲットとしたがんワクチン療法の開発 (2016)
  • Author(s): 水本有紀、勝田将裕、宮澤基樹、北畑裕司、津村亜矢子、宮本篤、尾島敏康、中森幹人、松田健司、早田啓治、邊見弘明、改正恒康、山上裕機
  • Organizer: 第27回 日本消化器癌発生学会総会
  • Place of Presentation: 鹿児島（鹿児島）
  • Year and Date: 2016-09-15
• [Presentation] Clec9A-mediated induction of Tfh and B cell responses. (2016)
  • Author(s): Y. Kato, M. Lahoud, T. Kaisho, K. Shortman, S. Mueller, I. Caminschi, W. Heath.
  • Organizer: International Congress of Immunology
  • Place of Presentation: (Melbourne, Australia)
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Involvement of XCR1-expressing dendritic cells through the XCR1-XCL1 chemokine axis in intestinal immune homeostasis. (2016)
  • Author(s): T. Ohta, H. Hemmi, T. Kaisho.
  • Organizer: International Congress of Immunology
  • Place of Presentation: (Melbourne, Australia)
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] XCR1＋樹状細胞をターゲットとした新規がんペプチドワクチン療法の開発 (2016)
  • Author(s): 水本有紀、勝田将裕、宮澤基樹、北畑裕司、津村亜矢子、尾島敏康、中森幹人、邊見弘明、改正恒康、山上裕機
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: 徳島（徳島）
  • Year and Date: 2016-07-14
• [Presentation] Homeostatic roles of intestinal dendritic cells expressing a chemokine receptor, XCR1, and XCL1-XCR1 chemokine system. (2016)
  • Author(s): T. Ohta, H. Hemmi, T. Kaisho.
  • Organizer: The 24th International Symposium on Molecular Cell Biology of Macrophages
  • Place of Presentation: (Tokyo, Japan)
  • Year and Date: 2016-06-03
  • Int'l Joint Research
• [Presentation] XCR1＋樹状細胞をターゲットとした新規がんペプチドワクチン療法の開発 (2016)
  • Author(s): 水本有紀、勝田将裕、宮澤基樹、北畑裕司、津村亜矢子、宮本篤、尾島敏康、中森幹人、松田健司 早田啓治、改正恒康、山上裕機
  • Organizer: 第37回 癌免疫外科研究会
  • Place of Presentation: 埼玉（川越）
  • Year and Date: 2016-05-12
• [Presentation] Critical roles of a dendritic cell subset expressing a chemokine receptor, XCR1. (2016)
  • Author(s): T. Kaisho
  • Organizer: Mechanisms of Molecular and Cellular Immunity
  • Place of Presentation: (Berlin, Germany)
  • Int'l Joint Research / Invited
• [Presentation] CD8 T cells orchestrate pDC-XCR1 DC spatial and functional cooperativity to optimize priming. (2016)
  • Author(s): A. Brewitz, S. Eickhoff, S. Dahling, T. Quast, S. Bedoui, R. A. Kroczek, C. Kurts, N. Garbi, T. Kaisho, W. Kolanus, M. Colonna, M. lannacone, R. N. Germain and W. Kastenmuller.
  • Organizer: 4th Cluster Science Days
  • Place of Presentation: (Bonn, Germany)
  • Int'l Joint Research
• [Presentation] How do XCR1-expressing dendritic cells function in vivo? (2016)
  • Author(s): T. Kaisho
  • Organizer: 4th Cluster Science Days
  • Place of Presentation: (Bonn, Germany)
  • Int'l Joint Research / Invited
• [Presentation] Intestinal immune homeostasis regulated by a dendritic cell subset expressing a chemokine, XCR1. (2016)
  • Author(s): T. Kaisho, T. Ohta, I. Sasaki, T. Orimo, T. Kato and H. Hemmi.
  • Organizer: Shandong-Wakayama Medical & Nursing Plenary Lecture 2016
  • Place of Presentation: (Wakayama, Japan)
  • Invited
• [Presentation] Dynamic control of inflammatory signaling by organelles in DC/macrophages. (2016)
  • Author(s): T. Kaisho
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄（宜野湾）
  • Invited
• [Presentation] XCR1+樹状細胞をターゲットとした新規がんペプチドワクチン療法の開発 (2015)
  • Author(s): 水本有紀、勝田将裕、宮澤基樹、北畑裕司、津村亜矢子、尾島敏康、早田啓治、北谷純也、堀田司、松田健司、改正恒康、山上裕機
  • Organizer: 第28回日本バイオセラピィ学会学術集会総会
  • Place of Presentation: Saitama, Japan
  • Year and Date: 2015-12-03
• [Presentation] In vivo behavior and functions of a dendritic cell subset expressing a chemokine receptor, XCR1. (2015)
  • Author(s): T. Kaisho
  • Organizer: Shandong University-Wakayama Medical University Medical and Nursing Symposium
  • Place of Presentation: Shandong, China
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Effective anti-tumor immunity provoked by chemokine-directed delivering to a DC subset with high CTL-inducing ability. (2015)
  • Author(s): Y. Mizumoto, H. Hemmi, M. Katsuda, T.Ohta, Y. Fukuda, H, Yamaue, T. Kaisho.
  • Organizer: 第44回日本免疫学会総会
  • Place of Presentation: Hokkaido, Japan
  • Year and Date: 2015-11-18
• [Presentation] Role of the polyamine pathway in Choleta toxin-induces production of proinflammatory cytokines. (2015)
  • Author(s): T. Orimo, I. Sasaki, S. Fukuda, H. Hemmi, Y. Fukuda, T. Kaisho.
  • Organizer: 第44回日本免疫学会総会
  • Place of Presentation: Hokkaido, Japan
  • Year and Date: 2015-11-18
• [Presentation] Fbxo21, a component of ubiquitin E3 ligase complex, associates with PDLIM2 and specifically rerulates NF-κB-mediated inflammatory sighnaling. (2015)
  • Author(s): T. Tanaka, A. Shibazaki, R. Ono, T. Kaisho.
  • Organizer: 第44回日本免疫学会総会
  • Place of Presentation: Hokkaido, Japan
  • Year and Date: 2015-11-18
• [Presentation] Intestinal immune homeostasis is regulated by XCR1-expressing dendritic cells through XCL1-XCR1 axis. (2015)
  • Author(s): T. Ohta, H. Hemmi, T. Kaisho.
  • Organizer: LC2015 14th Intermnational Workshop on Langerhans Cells
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-11-05
  • Int'l Joint Research
• [Presentation] Intestinal Immune Homeostasis Regulated by Dendritic Cells. (2015)
  • Author(s): 改正恒康
  • Organizer: The 3rd Homeostatic Inflammation International Symposium
  • Place of Presentation: 東京
  • Year and Date: 2015-01-31
  • Invited
• [Presentation] 樹状細胞を介した新規の生体恒常性維持機構 (2014)
  • Author(s): 改正恒康
  • Organizer: 第50回高血圧関連疾患モデル学会学術総会
  • Place of Presentation: 和歌山
  • Year and Date: 2014-12-05
  • Invited
• [Presentation] Regulatory mechanisms for inflammatory cytokine production by metabolic pathways. (2014)
  • Author(s): 改正恒康
  • Organizer: 第87回日本生化学会大会 The 87th Annual Meeting of the Japanese Biochemical Society
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-10-16
  • Invited
• [Remarks] 和歌山県立医科大学 先端医学研究所 生体調節機構研究部 公式ホームページ
  • URL: http://www.wakayama-med.ac.jp/dept/igakubu/1606032/index.html
• [Remarks] 和歌山県立医科大学 先端医学研究所 生体調節機構研究部 研究室ホームページ
  • URL: http://www.wakayama-med.ac.jp/med/seitai/index.php
• [Remarks]
  • URL: http://www.wakayama-med.ac.jp/med/seitai/