| First Author | Sung EA | Year | 2024 |
| Journal | Biochem Biophys Res Commun | Volume | 695 |
| Pages | 149441 | PubMed ID | 38176174 |
| Mgi Jnum | J:359893 | Mgi Id | MGI:7575417 |
| Doi | 10.1016/j.bbrc.2023.149441 | Citation | Sung EA, et al. (2024) Low-density lipoprotein receptor-related protein 6 ablation in macrophages differentially inhibits lung injury-mediated inflammation and metastasis. Biochem Biophys Res Commun 695:149441 |
| abstractText | Low-density lipoprotein receptor-related protein 6 (LRP6) is a receptor protein for Wnt ligands. Yet, their role in immune cell regulation remains elusive. Here we demonstrated that genetic deletion of LRP6 in macrophages using LysM-cre Lrp6(fl/fl) (Lrp6(MKO)) mice showed differential inhibition of inflammation in the bleomycin (BLM)-induced lung injury model and B16F10 melanoma lung metastasis model. Lrp6(MKO) mice showed normal immune cell populations in the lung and circulating blood in homeostatic conditions. In the BLM-induced lung injury model, Lrp6(MKO) mice showed a decreased number of monocyte-derived alveolar macrophages, reduced collagen deposition and alpha-smooth muscle actin (alphaSMA) protein levels in the lung. In B16F10 lung metastasis model, Lrp6(MKO) mice reduced lung tumor foci. Monocytic and granulocytic-derived myeloid-derived suppressor cells (M-MDSCs and G-MDSCs) were increased in the lung. In G-MDSCs, hypoxia-inducible factor 1alpha (HIF1alpha)(+) PDL1(+) population was markedly decreased but not in M-MDSCs. Taken together, our results show that the role of LRP6 in macrophages is differential depending on the inflammation microenvironment in the lung. |
