Analysis of phagocytic activity of aging macrophage and the accompanying inflammatory response induced by apoptotic cells

• Project/Area Number: 18K07183
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Toho University
• Principal Investigator: NAGATA Kisaburo 東邦大学, 理学部, 教授 (10291155)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 老化 / マクロファージ / 炎症応答 / アポトーシス / 炎症 / 貪食

Outline of Final Research Achievements

In this study, we investigated the mechanism of the decrease in phagocytic ability of macrophages accompanying aging. It was found that resident macrophages become pre-activated with aging, and their phagocytic ability decreases. In addition, it was suggested that the activation does not depend on the aging environment of the individual, but is caused by cell aging, and it was clarified that inactivation of p53 is involved in part of it.

Academic Significance and Societal Importance of the Research Achievements

本研究は、老化に伴って罹患率が著しく高くなる自己免疫疾患や多臓器機能不全の原因として、残存する死細胞に着目して展開した研究であり、老化に伴って死細胞が残存すると、持続的な炎症応答が誘発され、様々な疾病を起こしやすくなることを示し、その原因がマクロファージの活性化によるものであることを明らかにした。本研究の成果は、老化に伴うマクロファージの活性化を制御し、加齢に伴う様々な疾病の発症を抑えることを目指す足がかりにあるものと考えられる。

Research Products

• [Journal Article] RSV infection-elicited high MMP-12 producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration. (2021)
  • Author(s): 1.Makino, A., Shibata, T., Nagayasu, M., Hosoya, I., Nishimura, T., Nakano, C., Nagata, K., Ito, T., Takahashi,Y. and Nakamura S.
  • Journal Title: iScience Volume: 24 Issue: 10 Pages: 103201-103201
  • DOI: 10.1016/j.isci.2021.103201
  • Peer Reviewed
• [Journal Article] Respiratory Syncytial Virus Infection Exacerbates Pneumococcal Pneumonia via Gas6/Axl-mediated Macrophage Polarization (2020)
  • Author(s): Shibata T, Makino A, Ogata R, Nakamura S, Ito T, Nagata K, Terauchi Y, Oishi T, Fujieda M, Takahashi Y, Ato M.
  • Journal Title: J Clin Invest . Volume: 6 Issue: 6 Pages: 3021-3037
  • DOI: 10.1172/jci125505
  • NAID: 120007017546
  • Peer Reviewed / Open Access
• [Journal Article] Vitamin C deficiency causes muscle atrophy and a deterioration in physical performance. (2019)
  • Author(s): Takizawa, S., Funakoshi, T., Yatsu, T., Nagata, K., Aigaki, T., Machida, S., and Ishigami. A
  • Journal Title: Sci. Rep. Volume: 9 Issue: 1 Pages: 4702-4702
  • DOI: 10.1038/s41598-019-41229-7
  • NAID: 130007919173
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Protective effect of pre- and post-vitamin C treatments on UVB-irradiation-induced skin damage. (2018)
  • Author(s): Kawashima, S., Funakoshi, T., Sato, Y., Saito, N., Ohsawa, H., Kurita K., Nagata, K., Yoshida, M., and Ishigami. A.
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 16199-16199
  • DOI: 10.1038/s41598-018-34530-4
  • NAID: 130007893014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Changes in the function and phenotype of resident peritoneal macrophagesafter housing in an enriched environment. (2018)
  • Author(s): Otaki, M., Hirano, T., Yamaguchi, Y., Kaida, K., Koshika, S., Nagata, K., Nishimura, M., Kakinuma, S., Shimada, Y., and Kobayashi, K.
  • Journal Title: Int. Immunopharmac. Volume: 65 Pages: 44-49
  • DOI: 10.1016/j.intimp.2018.09.037
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] PHLDA1, another PHLDA family protein that inhibits Akt. (2018)
  • Author(s): Chen, Y., Takikawa, M., Tsutsumi, S., Yamaguchi, Y., Okabe, A., Shimada, M., Kawase, T., Sada, A., Ezawa, I., Takano, Y., Nagata, K. Suzuki, Y., Semba, K., Aburatani, H., and Ohki, R.
  • Journal Title: Cancer Sci Volume: 109 Issue: 11 Pages: 3532-3542
  • DOI: 10.1111/cas.13796
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Increased matrix metalloproteinase-12 respiratory syncytial virus indection leads to the exacerbation os asthma (2019)
  • Author(s): Makino A, Nagata K, Ito T, Takahashi Y, Shibata T.
  • Organizer: 日本免疫学会
• [Presentation] 老化に伴うマクロファージ貪食能低下と細胞老化の関わり (2018)
  • Author(s): 小鹿成二、皆田皓平、山口陽子、石神昭人、永田喜三郎
  • Organizer: 第41回日本分子生物学会
• [Presentation] 下垂体神経内分泌腫瘍で同定されたがん抑制遺伝子PHLDA3変異の機能解析 (2018)
  • Author(s): 冨永航平、永田喜三郎、大木美恵子
  • Organizer: 第41回日本分子生物学会
• [Presentation] p53はマクロファージのサイレントクリアランス機能を抑制する (2018)
  • Author(s): 山口陽子、皆田皓平、石神昭人、永田喜三郎
  • Organizer: 第41回日本分子生物学会
• [Presentation] アスコルビン酸欠乏がマウス骨格筋に及ぼす影響 (2018)
  • Author(s): 船越智子、滝沢晶子、谷津智史、永田喜三郎、相垣敏郎、町田修一、石神昭人
  • Organizer: 第41回日本分子生物学会
• [Presentation] 放射線被ばくによるマウスB細胞リンパ腫の発症リスクおよび遺伝子変異 (2018)
  • Author(s): 橘拓孝、臺野和広、森岡孝満、石川敦子、尚奕、金小海、小川真里、藤田美鈴、永田喜三郎、小林芳郎、野川宏幸、松浦彰、島田義也、柿沼志津子
  • Organizer: 第61回日本放射線影響学会
• [Presentation] 放射線誘発マウスTリンパ腫におけるIkarosのゲノム変異と関連するエピゲノム異常 (2018)
  • Author(s): 武井 怜奈、臺野 和広、砂押 正章、甘崎 佳子、森岡 孝満、永田喜三郎、野川 宏幸、松浦 彰、島田 義也、柿沼 志津子
  • Organizer: 第61回日本放射線影響学会
• [Book] スタンダード免疫学 (2018)
  • Author(s): 大谷真志、小林芳郎、笠原忠、築地信、永田喜三郎、渡邉直子
  • Total Pages: 242
  • Publisher: 丸善出版
  • ISBN: 9784621303382