Analysis of human senescence-related T cells using cohort study

• Project/Area Number: 15K15151
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: Hamazaki Yoko 京都大学, iPS細胞研究所, 教授 (10362477)
• Co-Investigator(Kenkyū-buntansha): 松田 文彦 京都大学, 医学研究科, 教授 (50212220)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: T細胞 / 細胞老化 / 免疫老化 / コホート研究 / Ｔ細胞老化 / 老化Ｔ細胞 / ゲノムコホート研究 / Ｔ細胞

Outline of Final Research Achievements

We obtained flow-cytometry data on immune cells from more than 200 healthy individuals in a cohort of people in Nagahama city, and are analyzing a possible correlation between immune cell phenotypes and laboratory values. In addition, we succeeded in identifying new age-related T cell subset (CXCR3+ naive phenotype CD8 T cells) using thymectomy mouse model and confirmed the existence of CD8 T cells with similar phenotypic and functional properties in human.

Research Products

• [Journal Article] Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice (2018)
  • Author(s): Suzuki H, Nagatake T, Nasu A, Lan H, Ikegami K, Setou M, Hamazaki Y, Kiyono H, Yagi K, Kondoh M, Kunisawa J
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 2904-2904
  • DOI: 10.1038/s41598-018-21120-7
  • NAID: 120006551757
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Combined effects of neoadjuvant letrozole and zoledronic acid on γδT cells in postmenopausal women with early-stage breast cancer (2018)
  • Author(s): Sugie Tomoharu、Suzuki Eiji、Yamauchi Akira、Yamagami Kazuhiko、Masuda Norikazu、Gondo Naomi、Sumi Eriko、Ikeda Takafumi、Tada Harue、Uozumi Ryuji、Kanao Shotaro、Tanaka Yoshimasa、Hamazaki Yoko、Minato Nagahiro、Toi Masakazu
  • Journal Title: Breast Volume: 38 Pages: 114-119
  • DOI: 10.1016/j.breast.2017.12.017
  • Peer Reviewed / Open Access
• [Journal Article] Bone Marrow Endothelial Cells Induce Immature and Mature B Cell Egress in Response to Erythropoietin (2017)
  • Author(s): Ito Takeshi、Hamazaki Yoko、Takaori-Kondo Akifumi、Minato Nagahiro
  • Journal Title: Cell Structure and Function Volume: 42 Issue: 2 Pages: 149-157
  • DOI: 10.1247/csf.17018
  • NAID: 130006251709
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed / Open Access
• [Journal Article] Physiologic Thymic Involution Underlies Age-Dependent Accumulation of Senescence-Associated CD4+T Cells (2017)
  • Author(s): Sato Kyosuke、Kato Aiko、Sekai Miho、Hamazaki Yoko、Minato Nagahiro
  • Journal Title: The Journal of Immunology Volume: 199 Issue: 1 Pages: 138-148
  • DOI: 10.4049/jimmunol.1602005
  • Peer Reviewed / Open Access
• [Journal Article] A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production (2017)
  • Author(s): Ohigashi I, Ohte Y, Setoh K, Nakase H, Maekawa A, Kiyonari H, Hamazaki Y, Sekai M, Sudo T, Tabara Y, Sawai H, Omae Y, Yuliwulandari R, Tanaka Y, Mizokami M, Inoue H, Kasahara M, Minato N, Tokunaga K, Tanaka K, Matsuda F, Murata S, Takahama Y.
  • Journal Title: JCI Insight Volume: 2 Issue: 10 Pages: 1-14
  • DOI: 10.1172/jci.insight.93664
  • NAID: 120006733720
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The potential role of Osteopontin in the maintenance of commensal bacteria homeostasis in the intestine. (2017)
  • Author(s): Ito K, Nakajima A1, Fukushima Y1, Suzuki K1, Sakamoto K, Hamazaki Y, Ogasawara K, Minato N, and Hattori M.
  • Journal Title: PLoS One. Volume: 12 Issue: 3 Pages: e0173629-e0173629
  • DOI: 10.1371/journal.pone.0173629
  • NAID: 120006488574
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A human PSMB11 variant affects molecular processing of thymoproteasome and thymic production of CD8+ T cells. (2017)
  • Author(s): Ohigashi, I, Ohte, Y, Setoh, K, Nakase, H, Maekawa, A, Kiyonari, H, Hamazaki, Y, Sekai, M, Sudo, T, Tabara, Y, Sawai, H, Omae, Y, Yuliwulandari, R, Tanaka, Y, Mizokami, M, Inoue, H, Kasahara, M, Minato, N, Tokunaga, K, Tanaka, K, Matsuda, F, Murata, S, and Takahama, Y.
  • Journal Title: J. Clin. Invest. Insight. Volume: in press
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Obesity accelerates T-cell senescence in visceral adipose tissue (2016)
  • Author(s): Shirakawa K, Yan X, Shinmura K, Endo J, Kataoka M, Katsumata Y, Yamamoto T, Anzai A, Isobe S, Yoshida N, Itoh H, Manabe I, Sekai M, Hamazaki Y, Fukuda K, Minato N, and Sano M.
  • Journal Title: J Clin Invest. Volume: 126 Issue: 12 Pages: 4626-4639
  • DOI: 10.1172/jci88606
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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] Medullary thymic epithelial stem cells: role in thymic epithelial cell maintenance and thymic involution (2016)
  • Author(s): Hamazaki Y, Sekai M, Minato N
  • Journal Title: Immunol Rev. Volume: 271 Issue: 1 Pages: 38-55
  • DOI: 10.1111/imr.12412
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Relb acts downstream of medullary thymic epithelial stem cells and is essential for the emergence of RANK+ medullary epithelial progenitors. (2016)
  • Author(s): Baik S, Sekai M, Hamazaki Y, Jenkinson WE, Anderson G.
  • Journal Title: Eur J Immunol. Volume: - Issue: 4 Pages: 857-62
  • DOI: 10.1002/eji.201546253
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Adult thymic epithelial cell (TEC) progenitors and TEC stem cells – Models and mechanisms for the development and maintenance of thymic epithelial cells (2015)
  • Author(s): Hamazaki Y.
  • Journal Title: Eur J Immunol. Volume: 45 Issue: 11 Pages: 2985-93
  • DOI: 10.1002/eji.201545844
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Adult thymic medullary epithelium is maintained and regenerated by lineage-restricted cells rather than bipotent progenitors (2015)
  • Author(s): Ohigashi I, Zuklys S, Sakata M, Mayer CE, Hamazaki Y, Minato N, Hollander GA, Takahama Y.
  • Journal Title: Cell Rep. Volume: 13 Issue: 7 Pages: 1432-43
  • DOI: 10.1016/j.celrep.2015.10.012
  • NAID: 120006727050
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A CD153+CD4+ T follicular cell population with cell-senescence features plays a crucial role in lupus pathogenesis via osteopontin production. (2015)
  • Author(s): 1.Tahir S, Fukushima Y, Sakamoto K, Sato K, Fujita H, Inoue J, Uede T, Hamazaki Y, Hattori M, Minato N.
  • Journal Title: The Journal of Immunology Volume: 194 Issue: 12 Pages: 5725-5735
  • DOI: 10.4049/jimmunol.1500319
  • Peer Reviewed / Open Access
• [Journal Article] Crucial role of the Rap G protein signal in Notch activation and leukemogenicity of T-cell acute lymphoblastic leukemia. (2015)
  • Author(s): Doi K, Imai T, Kressler C, Yagita H, Agata Y, Vooijs M, Hamazaki Y, Inoue J, Minato N.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 7978-7985
  • DOI: 10.1038/srep07978
  • NAID: 120005555511
  • Peer Reviewed / Open Access
• [Presentation] Thymic involution and immunosenescence (2018)
  • Author(s): 濱崎洋子
  • Organizer: 第 13回 国際長寿医療研究センター 国際シンポジウム 「老化研究の最前線」 炎症、免疫そして認知機能の集積回路
  • Int'l Joint Research / Invited
• [Presentation] 胸腺退縮と免疫老化 (2018)
  • Author(s): 濱崎洋子
  • Organizer: 第38回日本基礎老化学会シンポジウム 老化の多様性と加齢性疾患のメカニズム
  • Invited
• [Presentation] 免疫寛容とステルス性 (2018)
  • Author(s): 濱崎洋子
  • Organizer: 第１回 免疫ステルス公開シンポジウム
  • Invited
• [Presentation] Neutrophil recruitment and activation by Hassall’s corpuscles: Implications of “sterile inflammation” in the thymic medulla (2017)
  • Author(s): Jianwei Wang, Miho Sekai, Nagahiro Minato, and Yoko Hamazaki
  • Organizer: 7th international Workshop of Kyoto T cell conference
  • Place of Presentation: 京都大学 芝蘭会館（京都）
  • Year and Date: 2017-03-14
  • Int'l Joint Research
• [Presentation] Bone marrow endothelial cells cross-present blood-borne antigens to CD8+ T cells. (2017)
  • Author(s): Takeshi Ito, Yoko Hamazaki, and Nagahiro Minato
  • Organizer: 7th international Workshop of Kyoto T cell conference
  • Place of Presentation: 京都大学 芝蘭会館（京都）
  • Year and Date: 2017-03-14
  • Int'l Joint Research
• [Presentation] Reduced thymic output and subsequent homeostatic proliferation induce phenotypic changes and enhance proinflamatory traits in naïve CD8 T cells (2017)
  • Author(s): Aiko Kato, Yoko Hamazaki, Nagahiro Minato
  • Organizer: 7th international Workshop of Kyoto T cell conference
  • Place of Presentation: 京都大学 芝蘭会館（京都）
  • Year and Date: 2017-03-14
  • Int'l Joint Research
• [Presentation] Thymopoiesis regulates clonogenic activity of thymic epithelial cells (2017)
  • Author(s): Miho Sekai, Yoko Hamazaki, Nagahiro Minato
  • Organizer: 7th international Workshop of Kyoto T cell conference
  • Place of Presentation: 京都大学 芝蘭会館（京都）
  • Year and Date: 2017-03-14
  • Int'l Joint Research
• [Presentation] Innate immune cell recruitment and activation by Hassall’s corpuscles in the thymic medulla: Implications of “sterile inflammation” on T-cell development (2017)
  • Author(s): 濱崎洋子
  • Organizer: The RIKEN IMS-JSI International Symposium on Immunology 2017 “Decoding Immune Complexity from Cell to System”
  • Invited
• [Presentation] 中枢性自己寛容を保証する胸腺髄質上皮細胞の発生と機能に関する研究 (2017)
  • Author(s): 濱崎洋子
  • Organizer: 花王科学賞 受賞講演
  • Invited
• [Presentation] ハッサル小体が関与する胸腺内好中球活性化とその意義 (2017)
  • Author(s): 濱崎洋子
  • Organizer: 第３６回日本胸腺研究会 ミニシンポジウム
  • Invited
• [Presentation] Thymic involution in peripheral T cell homeostasis and immunosenescence (2017)
  • Author(s): 濱崎洋子
  • Organizer: Leibniz-AMED Workshop on Immune Regulation of Diseases and Aging
  • Invited
• [Presentation] 胸腺退縮に伴うＴ細胞の加齢変化とその意義 (2016)
  • Author(s): 濱崎洋子
  • Organizer: 脳心血管抗加齢研究会２０１６ シンポジウム「免疫老化から迫る脳心血管疾患の発症機序」
  • Place of Presentation: 秋葉原ＵＤＸ（東京）
  • Year and Date: 2016-12-18
  • Invited
• [Presentation] 胸腺における中枢性自己寛容の成立と胸腺退縮に伴うＴ細胞の加齢変化 (2016)
  • Author(s): 濱崎洋子
  • Organizer: CREATE 2015（Cardio-Renal Interaction and Translational Research Enhancement）
  • Place of Presentation: ロイヤルパークホテル （東京）
  • Year and Date: 2016-07-31
  • Invited
• [Presentation] Medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance (2016)
  • Author(s): Ｙｏｋｏ Ｈａｍａｚａｋｉ
  • Organizer: Swiss-Kyoto Joint Symposium “Understanding the Cellular and Molecular Mechanisms of the Robustness and Plasticity of Life”
  • Place of Presentation: 京都大学医学部・芝蘭会館（京都）
  • Year and Date: 2016-06-13
  • Int'l Joint Research / Invited
• [Presentation] 新たなＴ細胞産生の低下に伴う末梢Ｔ細胞の恒常性増殖は、ナイーブCD8 T細胞の質的変化を誘導し炎症応答を促進する (2016)
  • Author(s): 加藤愛子、濵﨑洋子、湊 長博
  • Organizer: Kyoto T cell conference 第26回学術集会
  • Place of Presentation: 延暦寺会館(京都)
  • Year and Date: 2016-05-20
• [Presentation] Medullary thymic epithelial stem cells ensuring lifelong T-cell tolerance (2016)
  • Author(s): Yoko Hamazaki
  • Organizer: The Fifth Bizan Immunology Symposium at University of Tokushima (BISUT5) “Immune System Development, Deviation, and Regulation”
  • Place of Presentation: Nichia Medical Hall, Kuramoto Campus, University of Tokushima (Tokushima)
  • Year and Date: 2016-03-03
  • Int'l Joint Research / Invited
• [Presentation] Medullary Thymic Epithelial Stem Cells Ensuring Lifelong Central T cell Tolerance (2016)
  • Author(s): Yoko Hamazaki
  • Organizer: Environment controlling normal and diseased hematopoietic and immune systems (Sponsored by MEXT Research Project on Analysis and Synthesis of Multidimensional Immune Organ Network and RIKEN IMS)
  • Place of Presentation: RIKEN Yokohama Research Institute 6F seminar room（Yokohama）
  • Year and Date: 2016-03-03
  • Int'l Joint Research / Invited
• [Book] 胸腺上皮幹細胞の早期活性低下に伴う胸腺退縮と免疫老化 (2017)
  • Author(s): 濱崎洋子、湊長博
  • Total Pages: 7
  • Publisher: 羊土社
• [Remarks] iPS細胞研究所
  • URL: http://www.cira.kyoto-u.ac.jp/
• [Remarks] iPS細胞研究所 主任研究者紹介
  • URL: http://www.cira.kyoto-u.ac.jp/j/research/hamazaki_summary.html