| First Author | Nakamoto S | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 4 | Pages | 5610-5627 |
| PubMed ID | 32112485 | Mgi Jnum | J:304953 |
| Mgi Id | MGI:6695416 | Doi | 10.1096/fj.201901955R |
| Citation | Nakamoto S, et al. (2020) EP3 signaling in dendritic cells promotes liver repair by inducing IL-13-mediated macrophage differentiation in mice. FASEB J 34(4):5610-5627 |
| abstractText | Macrophage plasticity is essential for liver wound healing; however, the mechanisms underlying macrophage phenotype switching are largely unknown. Dendritic cells (DCs) are critical initiators of innate immune responses; as such, they orchestrate inflammation following hepatic injury. Here, we subjected EP3-deficient (Ptger3(-/-) ) and wild-type (WT) mice to hepatic ischemia-reperfusion (I/R) and demonstrate that signaling via the prostaglandin E (PGE) receptor EP3 in DCs regulates macrophage plasticity during liver repair. Compared with WT mice, Ptger3(-/-) mice showed delayed liver repair accompanied by reduced expression of hepatic growth factors and accumulation of Ly6C(low) reparative macrophages and monocyte-derived DCs (moDCs). MoDCs were recruited to the boundary between damaged and undamaged liver tissue in an EP3-dependent manner. Adoptive transfer of moDCs from Ptger3(-/-) mice resulted in impaired repair, along with increased numbers of Ly6C(high) inflammatory macrophages. Bone marrow macrophages (BMMs) up-regulated expression of genes related to a reparative 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. |
