2023 Fiscal Year Final Research Report
Elucidation of the pathophysiology of colitis in CCR-deficient mice and establishment of a functional classification method for intestinal Th17 cells.
| Project/Area Number |
21K07984
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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 53010:Gastroenterology-related
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
村上 和成 大分大学, 医学部, 教授 (00239485)
小坂 聡太郎 大分大学, 医学部, 助教 (60835700)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 炎症性腸疾患 / Th17細胞 / ケモカイン受容体 / CCR2 / CCR6 |
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| Outline of Final Research Achievements |
We analyzed the pathophysiological function of the chemokine receptors CCR2 and CCR6 expressed on Th17 cells in intestinal inflammation and examined whether the expression pattern of CCRs can identify inflammatory and regulatory Th17 cells in the intestinal tissues. Intestinal inflammation in mice lacking CCR2 and CCR6 alone was exacerbated compared to wild-type mice, whereas that in CCR2/6 double-deficient mice was milder. CCR2+CCR6+Th17 cells produced high levels of the inflammatory cytokine, GM-CSF, and the amount of GM-CSF and the percentage of GM-CSF+Th17 cells in the colon were reduced in double-deficient mice. Taken together, these findings suggest that inflammatory Th17 cells are CCR2+CCR6+ cells and regulatory Th17 cells are CCR6 single-positive cells.
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| Free Research Field |
免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
クローン病や潰瘍性大腸炎などの炎症性腸疾患は、近年様々な分子標的薬による治療が行われているが、未だ治療が困難でありその病因の解明が必要である。今回、実験的大腸炎の病態形成におけるTh17細胞のケモカイン受容体CCR2とCCR6の生理的機能の一端が明らかになった。また、機能の異なるTh17細胞サブセットをCCR2とCCR6の発現パターンにより識別できる可能性が示された。今後、さらなる解析を進めることで、炎症性腸疾患の原因解明とTh17細胞サブセットを標的とした臨床応用が期待される。
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