Journal article
Tissue-resident CCR2+ macrophage TREM-1/3 signaling is necessary for monocyte and neutrophil recruitment to injured hearts
Cell reports (Cambridge), Vol.44(3), p.115380
03/25/2025
DOI: 10.1016/j.celrep.2025.115380
PMID: 40042972
Abstract
Triggering receptor expressed on myeloid cells 1 (TREM-1) has been shown to amplify inflammatory signals, such as Toll-like receptor signaling, after infection and sterile injury. While previous studies have demonstrated that TREM-1 activation in circulating immune cells promotes injury, the role of TREM-1 signaling in tissue-resident cells in the context of sterile inflammation remains poorly understood. Here, we used a cardiac transplantation model to dissect how Trem1/3 expression on heart-resident cells regulates sterile inflammation. TREM-1 is expressed in heart-resident C-C chemokine receptor 2 (CCR2)+ macrophages in mice and humans. TREM-1/3 signaling in tissue-resident CCR2+ macrophages promotes C-C motif chemokine ligand 3 (CCL3) production and is critical for recruiting neutrophils and CCR2+ monocytes after heart transplantation. We demonstrate prolonged allograft survival after transplantation of Trem1/3-deficient compared with wild-type hearts. We identify TREM-1/3 signaling in donor grafts as a potential future therapeutic target to blunt inflammation after myocardial ischemia-reperfusion injury.
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•Trem1/3 expression in CCR2+ cardiac macrophages drives production of inflammatory chemokines•Neutrophil/monocyte recruitment to transplanted hearts depends on graft Trem1/3 expression•Graft Trem1/3 expression enhances alloimmunity after heart transplantation
Outcomes after heart transplantation are limited by ischemia-reperfusion injury, a process driven by infiltration of immune cells. Terada et al. identify TREM-1/3 signaling in graft-resident CCR2+ macrophages as a critical driver of immune cell infiltration, graft injury, and rejection after heart transplantation.
Details
- Title: Subtitle
- Tissue-resident CCR2+ macrophage TREM-1/3 signaling is necessary for monocyte and neutrophil recruitment to injured hearts
- Creators
- Yuriko Terada - Washington University in St. LouisWenjun Li - Washington University in St. LouisJunedh M. Amrute - Washington University in St. LouisAmit I. Bery - Washington University in St. LouisCharles R. Liu - Washington University in St. LouisVenkatrao Nunna - Washington University in St. LouisChristian Corbin Frye - Washington University in St. LouisHao Dun - Washington University in St. LouisAndrew L. Koenig - Washington University in St. LouisHannah P. Luehmann - Washington University in St. LouisGyu Seong Heo - Washington University in St. LouisMacee C. Owen - Washington University in St. LouisAlexander N. Wein - Washington University in St. LouisYongjian Liu - Washington University in St. LouisJon H. Ritter - Washington University in St. LouisSumanth D. Prabhu - Washington University in St. LouisRuben G. Nava - Washington University in St. LouisAndrew E. Gelman - Washington University in St. LouisMarina Cella - Washington University in St. LouisMarco Colonna - Washington University in St. LouisKory J. Lavine - Washington University in St. LouisDaniel Kreisel - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.44(3), p.115380
- DOI
- 10.1016/j.celrep.2025.115380
- PMID
- 40042972
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 03/25/2025
- Academic Unit
- Stead Family Department of Pediatrics
- Record Identifier
- 9985161354302771
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