| First Author | Krishnan A | Year | 2024 |
| Journal | Sci Rep | Volume | 14 |
| Issue | 1 | Pages | 2145 |
| PubMed ID | 38273071 | Mgi Jnum | J:346029 |
| Mgi Id | MGI:7578462 | Doi | 10.1038/s41598-024-52710-3 |
| Citation | Krishnan A, et al. (2024) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) deletion in myeloid cells augments cholestatic liver injury. Sci Rep 14(1):2145 |
| abstractText | Ductular reactive (DR) cells exacerbate cholestatic liver injury and fibrosis. Herein, we posit that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) emanates from recruited macrophages and restrains DR cell expansion, thereby limiting cholestatic liver injury. Wild type (WT), Trail(fl/fl) and myeloid-specific Trail deleted (Trail(Deltamye)) C57BL/6 mice were exposed to DDC diet-induced cholestatic liver injury, which induced hepatomegaly and liver injury as compared to control diet-fed mice. However, parameters of liver injury, fibrosis, and inflammation were all increased in the Trail(Deltamye) mice as compared to the WT and Trail(fl/fl) mice. High dimensional mass cytometry indicated that cholestasis resulted in increased hepatic recruitment of subsets of macrophages and neutrophils in the Trail(Deltamye) mice. Spatial transcriptomics analysis revealed that the PanCK(+) cholangiocytes from Trail(Deltamye) mice had increased expression of the known myeloid attractants S100a8, Cxcl5, Cx3cl1, and Cxcl1. Additionally, in situ hybridization of Cxcl1, a potent neutrophil chemoattractant, demonstrated an increased expression in CK19(+) cholangiocytes of Trail(Deltamye) mice. Collectively, these data suggest that TRAIL from myeloid cells, particularly macrophages, restrains a subset of DR cells (i.e., Cxcl1 positive cells), limiting liver inflammation and fibrosis. Reprogramming macrophages to express TRAIL may be salutary in cholestasis. |
