| First Author | Kourtzelis I | Year | 2019 |
| Journal | Nat Immunol | Volume | 20 |
| Issue | 1 | Pages | 40-49 |
| PubMed ID | 30455459 | Mgi Jnum | J:282521 |
| Mgi Id | MGI:6381150 | Doi | 10.1038/s41590-018-0249-1 |
| Citation | Kourtzelis I, et al. (2019) DEL-1 promotes macrophage efferocytosis and clearance of inflammation. Nat Immunol 20(1):40-49 |
| abstractText | Resolution of inflammation is essential for tissue homeostasis and represents a promising approach to inflammatory disorders. Here we found that developmental endothelial locus-1 (DEL-1), a secreted protein that inhibits leukocyte-endothelial adhesion and inflammation initiation, also functions as a non-redundant downstream effector in inflammation clearance. In human and mouse periodontitis, waning of inflammation was correlated with DEL-1 upregulation, whereas resolution of experimental periodontitis failed in DEL-1 deficiency. This concept was mechanistically substantiated in acute monosodium-urate-crystal-induced inflammation, where the pro-resolution function of DEL-1 was attributed to effective apoptotic neutrophil clearance (efferocytosis). DEL-1-mediated efferocytosis induced liver X receptor-dependent macrophage reprogramming to a pro-resolving phenotype and was required for optimal production of at least certain specific pro-resolving mediators. Experiments in transgenic mice with cell-specific overexpression of DEL-1 linked its anti-leukocyte-recruitment action to endothelial cell-derived DEL-1 and its efferocytic/pro-resolving action to macrophage-derived DEL-1. Thus, the compartmentalized expression of DEL-1 facilitates distinct homeostatic functions in an appropriate context that can be harnessed therapeutically. |
