| Project/Area Number |
18K15812
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Mari Murakami 大阪大学, 医学系研究科, 助教 (10801293)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 炎症性腸疾患 / 獲得免疫 / シングルセル解析 / ヒト腸管粘膜固有層 / 腸管免疫 |
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| Outline of Final Research Achievements |
T cells differentiate into highly diverse subsets and display plasticity depending on the unique environment. Here, we identify the T cell subsets predominantly expanded in each subtype of Inflammatory bowel disease (IBD). Mass cytometry analysis in IBD patients reveals that Crohn’s disease (CD) and ulcerative colitis (UC) are characterized by the distinct patterns of T cell profiles: CD-predominant subcluster shows tissue-resident effector memory phenotype, while UC are predominated by recirculating lymphocytes with naive phenotype and follicular helper T cells. Subsequent profiling by single cell RNA-sequencing analysis reveals that CD-predominant T cell subset displays transcriptional signatures of natural cytotoxicity as well as effector activities at a single cell level. The imbalance between the key transcriptional programs which regulate differentiation toward specific T cell lineages underlies the distinct phenotype of CD and UC.
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| Academic Significance and Societal Importance of the Research Achievements |
炎症性腸疾患では病変局所において疾患特異的な免疫細胞が局在し、病態の形成に関与していると考えられる。したがって、疾患特異的免疫細胞を同定し、その機能解析を行うことにより、病態や治療標的が明らかにできる可能性がある。本研究において、我々は炎症性腸疾患において増加し、病態に関与するT細胞とその遺伝学的特徴を明らかにすることができた。さらに、そのT細胞を介する炎症のシグナル経路や、臨床所見との関連性を明らかにできたことから、学術的意義は大きく、今後の治療標的の開発につながる可能性がある。
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