2021 Fiscal Year Final Research Report
Mechanism of human B cell differentiation via amino-acid metabolism -Development of novel therapy for systemic lupus erythematosus-
Project/Area Number |
19K08900
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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Research Institution | University of Occupational and Environmental Health, Japan |
Principal Investigator |
Iwata Shigeru 産業医科大学, 医学部, 講師 (60389434)
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Co-Investigator(Kenkyū-buntansha) |
田中 良哉 産業医科大学, 医学部, 教授 (30248562)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | SLE / B細胞 / 自己免疫疾患 / 免疫代謝 |
Outline of Final Research Achievements |
The mechanism of lymphocytes differentiation in rheumatoid arthritis (RA) and systemic lupus erythemtosus (SLE) were assessed in a view of immunometabolism. We found that effector Th1 cells overproducing IFN-γ were involved in refractory to conventional therapy in SLE. These cells showed metabolic abnormalities such as mTOR activation, enhancement of aerobic glycolysis and lipid metabolism. We also found that essential amino-acid methionine was involved in the pathogenesis of SLE via mTOR activation and plasmablast differentiation in B cells. In addition, we found that there were abnormality of mitochondrial membrane potential , and enhancement of mitochondrial function via glutaminolysis was important for plasmablast differentiation in B cells from SLE.
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Free Research Field |
リウマチ・膠原病
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Academic Significance and Societal Importance of the Research Achievements |
今回、SLE患者のリンパ球分化誘導機構を、本邦では依然未開拓な細胞内代謝システムの観点から一部解明することできた。これらの研究結果により、従来SLE患者で示されてきた古典的経路(B細胞受容体、共刺激分子: CD40など、Toll様受容体、サイトカインなどによるシグナル伝達経路)によるリンパ球活性化機序に加え、新たに免疫代謝機構の関与が明らかとなり、さらに疾患活動性や自己抗体産生、治療抵抗性など病態に深く関与することも示された。今後、より正確な分子生物学的評価方法の確立、新規治療へ繋げていくとともに、慢性ウイルス感染症 ( C型肝炎)、多発性硬化症、癌治療など他分野への応用も期待される。
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