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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 PMC
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Developmental Endothelial Locus-1; Gingival Crevicular Fluid; Resolving Lipid Mediators; Apoptotic Cells; Resolution-phase; Mast-cells; In-vitro; Receptor; Periodontitis; Model
Sprache englisch
Veröffentlichungsjahr 2019
Prepublished im Jahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Zeitschrift Nature Immunology
Quellenangaben Band: 20, Heft: 1, Seiten: 40-49 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort 75 Varick St, 9th Flr, New York, Ny 10013-1917 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pancreatic Islet Research (IPI)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502600-002
G-502600-008
DOI 10.1038/s41590-018-0249-1
WOS ID WOS:000456273900013
Scopus ID 85056869028
PubMed ID 30455459
Erfassungsdatum 2018-12-03
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