By the same authors

From the same journal

DEL-1 promotes macrophage efferocytosis and clearance of inflammation

Research output: Contribution to journalArticlepeer-review

Published copy (DOI)

Author(s)

  • Xiaofei Li
  • Ioannis Mitroulis
  • Daniel Grosser
  • Tetsuhiro Kajikawa
  • Baomei Wang
  • Michal Grzybek
  • Janusz von Renesse
  • Aleksander Czogalla
  • Maria Troullinaki
  • Anaisa Ferreira
  • Christian Doreth
  • Klara Ruppova
  • Lan-Sun Chen
  • Kavita Hosur
  • Jong-Hyung Lim
  • Kyoung-Jin Chung
  • Sylvia Grossklaus
  • Anne Kathrin Tausche
  • Leo A B Joosten
  • Niki M Moutsopoulos
  • Ben Wielockx
  • Antonio Castrillo
  • Jonathan M Korostoff
  • Ünal Coskun
  • George Hajishengallis
  • Triantafyllos Chavakis

Department/unit(s)

Publication details

JournalNature immunology
DateAccepted/In press - 26 Sep 2018
DateE-pub ahead of print - 19 Nov 2018
DatePublished (current) - Jan 2019
Issue number1
Volume20
Number of pages10
Pages (from-to)40-49
Early online date19/11/18
Original languageEnglish

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-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.

    Research areas

  • Adult, Animals, Carrier Proteins/genetics, Cellular Reprogramming, Cytokines/metabolism, Gene Expression Regulation, Humans, Inflammation/chemically induced, Intercellular Signaling Peptides and Proteins, K562 Cells, Liver X Receptors/metabolism, Macrophages/physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Neutrophils/immunology, Periodontitis/immunology, Phagocytosis

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations