2023 Fiscal Year Final Research Report
Analysis of the mechanism of senescence-associated T cell accumulation in the salivary gland with aging.
Project/Area Number |
20K18494
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 57020:Oral pathobiological science-related
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Research Institution | Showa University (2021-2023) National Center for Geriatrics and Gerontology (2020) |
Principal Investigator |
Kurosawa Mie 昭和大学, 歯学部, 助教 (70815802)
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Project Period (FY) |
2020-04-01 – 2024-03-31
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Keywords | 唾液腺 / 免疫老化 / 細胞老化 |
Outline of Final Research Achievements |
In this study, to clarify the mechanism of dry mouth (xerostomia) caused by aging or Sjogren’s Syndrome (SS), we used aged mice or young aly/aly, a model of SS, mice. we found that the accumulation of senescence-associated T cells (SA-Ts) related with dry mouths were observed in the salivary gland (SG) of both aged mice and aly/aly mice. To reveal the mechanism of SA-Ts accumulation, we focused on the epithelial cells in the SG. Epithelial cells of aged mice expressed senescence marker gene and Cxcl13 but that of aly/aly mice expressed oxidative stress gene and Cxcl12. These results suggest that SA-Ts accumulation was occurred via engagement of CXCR13/CXCR5 triggered by aging in aged mice and CXCL12/CXCR4 triggered by oxidative stress in aly/aly mice.
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Free Research Field |
老化
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Academic Significance and Societal Importance of the Research Achievements |
加齢とシェーグレン症候群における口腔乾燥症は共にSA-T細胞の集積によって腺房細胞が破壊され、唾液量が減少することで発症する可能性が示唆された。しかし、加齢に伴う唾液腺へのSA-T細胞の集積は性ホルモンの影響を強く受ける可能性がある。唾液腺上皮細胞におけるエストロゲン添加ではCXCL13などの発現に影響を与えないことから、女性ホルモンであるエストロゲンは免疫細胞に影響を与える可能性がある。一方シェーグレン症候群モデルマウスの唾液腺上皮細胞では酸化ストレスのマーカーが上昇することから、加齢とシェーグレン症候群では、唾液腺にT細胞が集積するメカニズムが異なり、治療方針も異なる可能性が示唆された。
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