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Title: DEL-1 promotes macrophage efferocytosis and clearance of inflammation
Authors: Kourtzelis, Ioannis
Li, Xiaofei
Mitroulis, Ioannis
Grosser, Daniel
Kajikawa, Tetsuhiro
Wang, Baomei
Grzybek, Michal
von Renesse, Janusz
Czogalla, Aleksander
Troullinaki, Maria
Ferreira, Anaisa
Doreth, Christian
Ruppova, Klara
Chen, Lan Sun
Hosur, Kavita
Lim, Jong Hyung
Chung, Kyoung Jin
Grossklaus, Sylvia
Tausche, Anne Kathrin
Joosten, Leo A.B.
Moutsopoulos, Niki M.
Wielockx, Ben
Castrillo, Antonio 
Korostoff, Jonathan M.
Coskun, Ünal
Hajishengallis, George
Chavakis, Triantafyllos
Keywords: Developmental Endothelial Locus-1
Gingival Crevicular Fluid
Resolving Lipid Mediators
Apoptotic Cells
Resolution-Phase, et al
Issue Date: 2019
Publisher: 1529-2908
Journal: Nature Immunology 
Abstract: 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-crystalinduced 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 proresolving 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.
ISSN: 1529-2908
DOI: 10.1038/s41590-018-0249-1
Source: Nature Immunology[ISSN 1529-2908],v. 20, p. 40-49
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