2021 Fiscal Year Final Research Report
Circadian clock and proliferative metabolism in the intestinal T lymphocytes
| Project/Area Number |
19K09012
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
土居 雅夫 京都大学, 薬学研究科, 教授 (20432578)
宮下 和季 慶應義塾大学, 医学部(信濃町), 特任准教授 (50378759)
三上 洋平 慶應義塾大学, 医学部(信濃町), 講師 (80528662)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 概日リズム / 概日時計 / 代謝 / エピジェネティックス |
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| Outline of Final Research Achievements |
Circadian rhythms are heavily involved in metabolic homeostasis. Circadian misalignment is implicated in a wide array of pathophysiology such as cancer, metabolic syndrome, and sleep disruption. This study dissected whether the circadian clock controls proliferative metabolism in activated T lymphocytes. The proportion of splenic T lymphocyte subset population was comparable between the wild-type and Bmal1 knock out mice. On the other hand, when naive T cells (Tn) were isolated, cultured, and stimulated by CD3/28 antibody, Tn from Bmal1 knockout mice exhibited higher proliferative capacity and numbers of cells. Additionally, expression of genes encoding components of glycolysis and glutamine oxidation along with that of MYC protein was upregulated.
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| Free Research Field |
内分泌代謝学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の知見より、T細胞活性化の際の増殖代謝と体内時計が関与することが示唆されている。概日リズム異常は、慢性炎症や自己免疫を増悪する可能性が示唆されているが、大腸癌や炎症性腸疾患、肥満や糖尿病などにおいても、概日時計変容が関与することから、T細胞の概日時計が免疫機能を通じて消化器疾患や内分泌代謝疾患に関与する可能性が考えられる。引き続き、今後詳細な機序を検討することによって、腸管免疫を介した炎症性腸疾患や大腸癌、代謝疾患の創薬ターゲットを探索も目指していく方針である。
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