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Cited by 306

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DEL-1 promotes macrophage efferocytosis and clearance of inflammation

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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·2019·Nature Immunology
DOI 10.1038/s41590-018-0249-1
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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. DEL-1 protein interferes with leukocyte adhesion to prevent inflammation. Chavakis and colleagues now show that DEL-1 contributes to tissue resolution after inflammation by promoting macrophage-mediated efferocytosis and M2-like pro-resolving activities.

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Metadata

Authors
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.
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2018-11-19
Volume
20
Issue
1
Pages
40-49
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/s41590-018-0249-1
OpenAlex
W2899909210
Cited by
306
References
11
FWCI
7.67
Type
journal article
Language
en
Open access
green
Licence
www.springer.com/tdm (tdm)

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CoChat. (2026). Citation check: DEL-1 promotes macrophage efferocytosis and clearance of inflammation. https://app.cochat.ai/papers/10.1038/s41590-018-0249-1
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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., . . . Chavakis, T. (2019). DEL-1 promotes macrophage efferocytosis and clearance of inflammation. Nature Immunology. https://doi.org/10.1038/s41590-018-0249-1

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