Elucidation of new control mechanisms of Bob1 in Th17 cells and its application to a disease-related marker
Project/Area Number |
19K16614
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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 49030:Experimental pathology-related
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Research Institution | Sapporo Medical University |
Principal Investigator |
Ippei Ikegami 札幌医科大学, 医学部, 助教 (80837021)
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Project Period (FY) |
2019-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | Bob1 / Th17 / EAE / Multiple Sclerosis / IL-17A |
Outline of Research at the Start |
難治性の自己免疫疾患の病態病理を解明し、診断方法、治療方法を確立することが社会的に求められている。我々はこれまでに転写共役因子Bob1がCD4陽性ヘルパーT細胞のうち抗体産生機構を司る濾胞ヘルパーT細胞に発現していることを初めて同定し、Bob1の機能的意義に着目している。更なる検討の結果、Bob1は濾胞ヘルパーT細胞だけでなく、他のCD4陽性T細胞サブセットにも発現していることを発見した。そこで本研究では、CD4陽性T細胞におけるBob1の機能制御機構の解明を目指す。本研究の成果を元に、CD4陽性T細胞が病態を形成する自己免疫疾患とBob1との関係を明らかにし、今後の臨床応用へと発展させたい。
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Outline of Final Research Achievements |
In this study, we performed functional analysis of the transcriptional coactivator Bob1 in CD4 positive (CD4+) T cells. We found that Bob1 knock out (KO) mice were resistant to experimental autoimmune encephalomyelitis (EAE) and the number of IL-17A-producing CD4+ T cell, which is involved in the pathogenesis of EAE, was decreased Bob1 KO mice compared to that in WT mice. These results suggest that Bob1 positively regulates IL-17A production in CD4+ T cells. We revealed new mechanisms that Bob1 enhances IL-17A expression by interacting with RORγt (Biochem Biophys Res Commun. 2019). Based on these results, we generated CD4+ T cell-specific Bob1 deficient mice further to know the role of Bob1 in CD4+ T cells in vivo.
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Academic Significance and Societal Importance of the Research Achievements |
Bob1はこれまでB細胞での機能的意義について検討されてきたが、本研究によりBob1はCD4陽性T細胞サブセットのうちTh17細胞のIL-17A産生に寄与すること見出した。Bob1は転写因子Oct1/2との結合様式が知られていたが、Th17細胞のマスター転写因子であるRORγtとBob1が結合し、転写活性を調節するという新規制御機構を初めて見出し、学術的に意義のある結果を得た。病原性CD4陽性T細胞の機能制御は不明な点が多いため、CD4陽性T細胞特異的Bob1欠損マウスを用いた研究により、CD4陽性T細胞が病態形成に寄与する疾患の理解が進み、得られた結果を医療社会に還元できると確信している。
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Report
(3 results)
Research Products
(5 results)
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[Journal Article] Activated circulating T follicular helper cells and skewing of T follicular helper 2 cells are down-regulated by treatment including an inhaled corticosteroid in patients with allergic asthma2020
Author(s)
Miyajima S, Shigehara K, Kamekura R, Takaki H, Yabe H, Ikegami I, Asai Y, Nishikiori H, Chiba H, Uno E, Takahashi H, Ichimiya S.
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Journal Title
Allergology International
Volume: 69
Issue: 1
Pages: 66-77
DOI
NAID
ISSN
1323-8930, 1440-1592
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cytotoxic Tph-like cells are involved in persistent tissue damage in IgG4-related disease.2020
Author(s)
Yabe H, Kamekura R, Yamamoto M, Murayama K, Kamiya S, Ikegami I, Shigehara K, Takaki H, Chiba H, Takahashi H, Takano K, Takahashi H, Ichimiya S.
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Journal Title
Mod Rheumatol.
Volume: Feb 5
Issue: 1
Pages: 1-12
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] IL-10+ T follicular regulatory cells are associated with the pathogenesis of IgG4-related disease.2019
Author(s)
Ito F, Kamekura R, Yamamoto M, Takano K, Takaki H, Yabe, H, Ikegami I, Shigehara K, Himi T, Takahashi H, Ichimiya S.
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Journal Title
Immunol Lett.
Volume: 207
Pages: 56-63
DOI
Related Report
Peer Reviewed / Open Access
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