Understanding for the mechanism of thymic involution during aging

• Project/Area Number: 19K16689
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Kyoto University (2020-2022); Hokkaido University (2019)
• Principal Investigator: Sekai Miho 京都大学, 医学研究科, 特定助教 (50737533)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 胸腺 / 免疫 / 退縮

Outline of Research at the Start

T 細胞を産生する組織である胸腺は、思春期以降に萎縮が始まり、加齢に伴いT 細胞産生能が低下する。この生理的な胸腺退縮は脂肪細胞の増大を伴い、末梢ではT 細胞の亜集団の割合や機能が変化することが知られている。しかし、脂肪細胞をはじめとする胸腺退縮に伴う変化がどのようにT細胞産生に寄与し得るのかはよくわかっていない。そこで本研究では、胸腺における脂肪細胞および胸腺上皮幹細胞の加齢変化の解明を通じて、生理的な胸腺退縮のメカニズムを明らかにする。

Outline of Final Research Achievements

The thymus is a central lymphoid organ essential for T-cell production. Although it is well known that the thymus involutes with age, the mechanism of the thymic involution remain unclear. We have previously identified thymic epithelial stem cells that support T cell development and demonstrated that the stem cell activity decline with age. In this study, we identified a T cell population that affects the activity of thymic epithelial stem cells and revealed the mechanism to regulate stem cell activity.

Academic Significance and Societal Importance of the Research Achievements

本研究は、胸腺上皮細胞の幹細胞の活性を評価できるコロニー培養系を確立し、それを用いて生理的な胸腺退縮メカニズムの一端を明らかにした。本コロニー培養系は、胸腺上皮幹細胞活性を制御するメカニズムの解明を可能にし、今後さらなる研究の推進に貢献できると期待される。また、特定のT細胞集団が胸腺上皮幹細胞を制御する分子メカニズムを明らかにすることで、胸腺退縮を制御できる可能性がある。これらの研究は、胸腺および免疫系の維持や制御についての理解に繋がると考えられる。

Research Products

• [Journal Article] Basal extrusion of single‐oncogenic mutant cells induces dome‐like structures with altered microenvironments (2022)
  • Author(s): Shirai Takanobu、Sekai Miho、Kozawa Kei、Sato Nanami、Tanimura Nobuyuki、Kon Shunsuke、Matsumoto Tomohiro、Murakami Takeru、Ito Shoko、Tilston‐Lunel Andrew、Varelas Xaralabos、Fujita Yasuyuki
  • Journal Title: Cancer Science Volume: 113 Issue: 11 Pages: 3710-3721
  • DOI: 10.1111/cas.15483
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells (2022)
  • Author(s): Kuromiya K, Aoki K, Ishibashi K, Yotabun M, Sekai M, Tanimura N, Iijima S, Ishikawa S, Kamasaki T, Akieda Y, Ishitani T, Hayashi T, Toda S, Yokoyama K, Lee CG, Usami I, Inoue H, Takigawa I, Gauquelin E, Sugimura K, Hino N, Fujita Y
  • Journal Title: Cell Reports Volume: 40 Issue: 2 Pages: 111078-111078
  • DOI: 10.1016/j.celrep.2022.111078
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The CD44/COL17A1 Pathway Plays a Vital Role in the Formation of Multilayered, Transformed Epithelia. (2021)
  • Author(s): Kozawa K, ,Sekai M, Ohba K, Ito S, Sako H, Maruyama T, Kakeno M , Kuromiya K, Kamasaki T, Kohashi K, Ishikawa S, Sato N, Asano S, Suzuki H, Tanimura N, Mukai Y, Gotoh N, Tanino M, Tanaka S Natsuga K, Soga T. Nakamura T, Yabuta Y, Saitou M, Ito T, Matsuura K, Tsunoda M,et.al..
  • Journal Title: Curr Biol Volume: 31 Issue: 14 Pages: 3086-3097
  • DOI: 10.1016/j.cub.2021.04.078
  • Peer Reviewed / Open Access
• [Journal Article] An improved clonogenic culture method for thymic epithelial cells (2019)
  • Author(s): Sekai Miho、Wang Jianwei、Minato Nagahiro、Hamazaki Yoko
  • Journal Title: Journal of Immunological Methods Volume: 467 Pages: 29-36
  • DOI: 10.1016/j.jim.2019.02.003
  • Peer Reviewed / Open Access
• [Journal Article] Clonogenic Culture of Mouse Thymic Epithelial Cells (2019)
  • Author(s): Sekai Miho、Wang Jianwei、Hamazaki Yoko
  • Journal Title: Methods Mol Biol. Volume: 2048 Pages: 143-153
  • DOI: 10.1007/978-1-4939-9728-2_15
  • ISBN: 9781493997275, 9781493997282
  • Peer Reviewed / Open Access
• [Journal Article] Hassall’s corpuscles with cellular-senescence features maintain IFNα production through neutrophils and pDC activation in the thymus (2018)
  • Author(s): Wang Jianwei、Sekai Miho、Matsui Takeshi、Fujii Yosuke、Matsumoto Mitsuru、Takeuchi Osamu、Minato Nagahiro、Hamazaki Yoko
  • Journal Title: International Immunology Volume: 31 Issue: 3 Pages: 127-139
  • DOI: 10.1093/intimm/dxy073
  • NAID: 120007164929
  • Peer Reviewed / Open Access