CCL5 promotes resolution-phase macrophage reprogramming in concert with the atypical chemokine receptor d6 and apoptotic polymorphonuclear cells

Miran Aswad, Simaan Assi, Sagie Schif-Zuck, Amiram Ariel

Research output: Contribution to journalArticlepeer-review

Abstract

The engulfment of apoptotic polymorphonuclear cells (PMN) during the resolution of inflammation leads to macrophage reprogramming culminating in reduced proinflammatory and increased anti-inflammatory mediator secretion. The atypical chemokine receptor D6/ACKR2 is expressed on apoptotic PMN and plays an important role in regulating macrophage properties during and after engulfment. In this study, we found that the inflammatory chemokine CCL5 is mostly retained (75%) during the resolution of zymosan A peritonitis in mice. Moreover, this chemokine is secreted by resolution-phase macrophages (2.5 ng/ml) and promotes their reprogramming in vivo in D6+/+ mice (2-fold increase in IL-10/IL-12 ratio) but not their D62/2 counterparts. In addition, CCL5 enhanced macrophage reprogramming ex vivo exclusively when bound to D6+/+ apoptotic PMN. Signaling through p38MAPK and JNK in reprogrammed macrophages was enhanced by CCL5-bound apoptotic PMN (3.6-4 fold) in a D6-dependent manner, and was essential for reprogramming. Thus, CCL5 exerts a novel proresolving role on macrophages when acting in concert with apoptotic PMN-expressed D6.

Original languageEnglish
Pages (from-to)1393-1404
Number of pages12
JournalJournal of Immunology
Volume199
Issue number4
DOIs
StatePublished - 15 Aug 2017

Bibliographical note

Funding Information:
This work was supported by grants from the Israel Science Foundation (Grant 534/ 09), the Rosetrees Trust, and the Wolfson Foundation.

Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc.

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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