biostudies-literatureTerada YBLRD VANIBIB NIH HHSNIAID NIH HHSNHLBI NIH HHSNIAMS NIH HHS115380https://www.ebi.ac.uk/biostudies/studies/S-EPMC12756909biostudies-literatureUnknown44(3)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 foCell reportsTissue-resident CCR2<sup>+</sup> macrophage TREM-1/3 signaling is necessary for monocyte and neutrophil recruitment to injured hearts.PMC12756909I01 BX002730P30 AR073752R35 HL161185R01 HL151078P01 AI116501R01 HL094601P41 EB025815R35 HL145212Nava RGGelman AEHeo GSColonna MWein ANLavine KJKreisel DBery AIPrabhu SDTerada YLi WDun HKoenig ALLiu YCella MLuehmann HPRitter JHLiu CROwen MCFrye CCAmrute JMNunna VfalseTissue-resident CCR2<sup>+</sup> macrophage TREM-1/3 signaling is necessary for monocyte and neutrophil recruitment to injured hearts.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 fo2025-01-01T00:00:00Z2025 Mar2026-06-09T05:17:14.318Z2026-06-09T03:07:44.353ZS-EPMC127569094004297210.1016/j.celrep.2025.115380