2022 Fiscal Year Final Research Report
Elucidating the Function of Chemokine CCL20 in Inflammatory Bowel Disease using Genome-Edited Mouse Models
| Project/Area Number |
20K17025
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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 | Oita University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | ケモカイン / 炎症性腸疾患 / ゲノム編集マウス / 疾患モデルマウス / CCL20 / CCR6 / CCR2 |
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| Outline of Final Research Achievements |
To elucidate the physiological role of chemokines and chemokine receptors in inflammatory bowel disease, CCL20-, CCR2- and CCR6-deficient mice were generated by genome editing and analyzed for DSS-induced colitis; all mutant mice showed more severe colitis than wild-type mice. The frequencies of CD4+ T cells in the Peyer's patches were reduced in CCL20-deficient mice compared to those in wild-type mice after DSS treatment. In contrast, when CCR2/CCR6 double-deficient mice were generated, DSS-induced colitis was conversely milder than wild-type mice. We found that CCR2+CCR6+Th17 cells in the colonic lamina propria produced high levels of GM-CSF, suggesting that the migration of these inflammatory Th17 cells is important in the pathogenesis of colitis.
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| Free Research Field |
消化器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
ダイナミックな免疫システムを理解するためには、白血球遊走を司るケモカインの役割を解明する必要がある。これまで、多発性硬化症や潰瘍性大腸炎の治療にα4インテグリン阻害薬が開発されており、今後もリンパ球のホーミングや遊走に関連した分子標的薬の開発が益々盛んになると考えられる。従って、ケモカインによる免疫制御機構の理解が自己免疫疾患の治療薬開発には欠かせないが、本研究により炎症性腸疾患におけるCCL20/CCR6およびCCR2の役割を分子生物学的手法を用いて個体レベルで明らかになったことは、学術的および社会的に意義が大きいと言える。
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