Hematopoietic ChemR23 (Chemerin Receptor 23) Fuels Atherosclerosis by Sustaining an M1 Macrophage-Phenotype and Guidance of Plasmacytoid Dendritic Cells to Murine Lesions-Brief Report

Emiel P. C. van der Vorst, Manuela Mandl, Madeleine Mueller, Carlos Neideck, Yvonne Jansen, Michael Hristov, Selin Gencer, Linsey J. F. Peters, Svenja Meiler, Micha Feld, Anna-Lena Geiselhoeringer, Renske J. de Jong, Caspar Ohnmacht, Heidi Noels, Oliver Soehnlein, Maik Drechsler, Christian Weber, Yvonne Doering*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Web of Science)

Abstract

Objective- Expression of the chemokine-like receptor ChemR23 (chemerin receptor 23) has been specifically attributed to plasmacytoid dendritic cells (pDCs) and macrophages and ChemR23 has been suggested to mediate an inflammatory immune response in these cells. Because chemokine receptors are important in perpetuating chronic inflammation, we aimed to establish the role of ChemR23-deficiency on macrophages and pDCs in atherosclerosis. Approach and Results- ChemR23-knockout/knockin mice expressing eGFP (enhanced green fluorescent protein) were generated and after crossing with apolipoprotein E-deficient (Apoe(-/-) ChemR23(e/e)) animals were fed a western-type diet for 4 and 12 weeks. Apoe(-/-) ChemR23(e/e) mice displayed reduced lesion formation and reduced leukocyte adhesion to the vessel wall after 4 weeks, as well as diminished plaque growth, a decreased number of lesional macrophages with an increased proportion of M2 cells and a less inflammatory lesion composition after 12 weeks of western-type diet feeding. Hematopoietic ChemR23-deficiency similarly reduced atherosclerosis. Additional experiments revealed that ChemR23-deficiency induces an alternatively activated macrophage phenotype, an increased cholesterol efflux and a systemic reduction in pDC frequencies. Consequently, expression of the pDC marker SiglecH in atherosclerotic plaques of Apoe(-/-) ChemR23(e/e) mice was declined. ChemR23-knockout pDCs also exhibited a reduced migratory capacity and decreased CCR (CC-type chemokine receptor)7 expression. Finally, adoptive transfer of sorted wild-type and knockout pDCs into Apoe(-/-) recipient mice revealed reduced accumulation of ChemR23-deficient pDCs in atherosclerotic lesions. Conclusions- Hematopoietic ChemR23-deficiency increases the proportion of alternatively activated M2 macrophages in atherosclerotic lesions and attenuates pDC homing to lymphatic organs and recruitment to atherosclerotic lesions, which synergistically restricts atherosclerotic plaque formation and progression.

Original languageEnglish
Pages (from-to)685-693
Number of pages9
JournalArteriosclerosis Thrombosis and Vascular Biology
Volume39
Issue number4
DOIs
Publication statusPublished - Apr 2019

Keywords

  • atherosclerosis
  • chemokines
  • chemokine receptor
  • dendritic cells
  • macrophages
  • mice
  • EXPRESSION
  • FAT
  • INFLAMMATION

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