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Kourtzelis, I.* ; Li, X.* ; Mitroulis, I.* ; Grosser, D. ; Kajikawa, T.* ; Wang, B.* ; Grzybek, M. ; von Renesse, J.* ; Czogalla, A.* ; Troullinaki, M.* ; Ferreira, A.* ; Doreth, C.* ; Ruppova, K.* ; Chen, L.S.* ; Hosur, K.* ; Lim, J.H.* ; Chung, K.-J. ; Grossklaus, S.* ; Tausche, A.K.* ; Joosten, L.A.B.* ; Moutsopoulos, N.M.* ; Wielockx, B.* ; Castrillo, A.* ; Korostoff, J.M.* ; Coskun, Ü. ; Hajishengallis, G.* ; Chavakis, T.*

DEL-1 promotes macrophage efferocytosis and clearance of inflammation.

Nat. Immunol. 20, 40-49 (2019)
Postprint DOI
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Developmental Endothelial Locus-1; Gingival Crevicular Fluid; Resolving Lipid Mediators; Apoptotic Cells; Resolution-phase; Mast-cells; In-vitro; Receptor; Periodontitis; Model
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Quellenangaben Volume: 20, Issue: 1, Pages: 40-49 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place 75 Varick St, 9th Flr, New York, Ny 10013-1917 Usa
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)