| Project/Area Number |
18K16373
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 55020:Digestive surgery-related
|
|---|
| Research Institution | Kitasato University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 肝修復 / 樹状細胞 / マクロファージ / 肝 / 再生 / 修復 / 免疫細胞 / 肝障害 |
|---|
| Outline of Final Research Achievements |
We clarified the role of PGE receptor, EP3 in dendritic cells (DCs) during liver repair by subjecting EP3-deficient (EP3-/-) and wild-type (WT) mice to hepatic ischemia-reperfusion (I/R). Compared with WT mice, EP3-/- mice showed delayed liver repair accompanied by reduced accumulation of reparative macrophages and monocyte-derived DCs (moDCs). Adoptive transfer of moDCs from EP3-/- mice resulted in impaired repair, along with increased inflammatory macrophages. Bone marrow macrophages (BMMs) up-regulated expression of genes related to a restorative macrophage phenotype when co-cultured with moDCs; this phenomenon was dependent on EP3 signaling. In the presence of an EP3 agonist, interleukin (IL)-13 derived from moDCs drove BMMs to increase expression of genes characteristic of a reparative macrophage phenotype. The results suggest that EP3 signaling in moDCs facilitates liver repair by inducing IL-13-mediated switching of macrophage phenotype from pro-inflammatory to pro-reparative.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究はプロスタグランジン/PGE受容体シグナルが従来の炎症誘導作用ではなく、肝組織修復・肝再生に関与している観点から、脂質メディエーターの果たす機能的役割を検証した。さらに、PGE受容体シグナルを介した肝修復に関与する細胞としてこれまで解明されたことのない肝樹状細胞に焦点を当て、新しい肝修復制御機構を明らかにすることができた。今後、脂質メディエーター制御による新規肝再生治療への開発や創薬など臨床応用につながる可能性があり、肝再生医学の研究領域の発展に貢献できる。
|
