| First Author | Goto T | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 754106 | PubMed ID | 34691073 |
| Mgi Jnum | J:312716 | Mgi Id | MGI:6785593 |
| Doi | 10.3389/fimmu.2021.754106 | Citation | Goto T, et al. (2021) Activation of iNKT Cells Facilitates Liver Repair After Hepatic Ischemia Reperfusion Injury Through Acceleration of Macrophage Polarization. Front Immunol 12:754106 |
| abstractText | Macrophage polarization is critical for liver tissue repair following acute liver injury. However, the underlying mechanisms of macrophage phenotype switching are not well defined. Invariant natural killer T (iNKT) cells orchestrate tissue inflammation and tissue repair by regulating cytokine production. Herein, we examined whether iNKT cells played an important role in liver repair after hepatic ischemia-reperfusion (I/R) injury by affecting macrophage polarization. To this end, we subjected male C57BL/6 mice to hepatic I/R injury, and mice received an intraperitoneal (ip) injection of alpha-galactosylceramide (alpha-GalCer) or vehicle. Compared with that of the vehicle, alpha-GalCer administration resulted in the promotion of liver repair accompanied by acceleration of macrophage differentiation and by increases in the numbers of Ly6C(high) pro-inflammatory macrophages and Ly6C(low) reparative macrophages. iNKT cells activated with alpha-GalCer produced interleukin (IL)-4 and interferon (IFN)-gamma. Treatment with anti-IL-4 antibodies delayed liver repair, which was associated with an increased number of Ly6C(high) macrophages and a decreased number of Ly6C(low) macrophages. Treatment with anti-IFN-gamma antibodies promoted liver repair, associated with reduced the number of Ly6C(high) macrophages, but did not change the number of Ly6C(low) macrophages. Bone marrow-derived macrophages up-regulated the expression of genes related to both a pro-inflammatory and a reparative phenotype when co-cultured with activated iNKT cells. Anti-IL-4 antibodies increased the levels of pro-inflammatory macrophage-related genes and decreased those of reparative macrophage-related genes in cultured macrophages, while anti-IFN-gamma antibodies reversed the polarization of macrophages. Cd1d-deficient mice showed delayed liver repair and suppressed macrophage switching, compared with that in wild-type mice. These results suggest that the activation of iNKT cells by alpha-GalCer facilitated liver repair after hepatic I/R injury by both IL-4-and IFN-gamma-mediated acceleration of macrophage polarization. Therefore, the activation of iNKT cells may represent a therapeutic tool for liver repair after hepatic I/R injury. |
