Tissue-resident CCR2⁺ macrophage TREM-1/3 signaling is necessary for monocyte and neutrophil recruitment to injured hearts.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-04 DOI:10.1016/j.celrep.2025.115380

Yuriko Terada, Wenjun Li, Junedh M Amrute, Amit I Bery, Charles R Liu, Venkatrao Nunna, Christian Corbin Frye, Hao Dun, Andrew L Koenig, Hannah P Luehmann, Gyu Seong Heo, Macee C Owen, Alexander N Wein, Yongjian Liu, Jon H Ritter, Sumanth D Prabhu, Ruben G Nava, Andrew E Gelman, Marina Cella, Marco Colonna, Kory J Lavine, Daniel Kreisel

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引用次数: 0

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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髓系细胞上表达的触发受体 1（TREM-1）已被证明能在感染和无菌损伤后放大炎症信号，如 Toll 样受体信号。以前的研究表明，循环免疫细胞中的 TREM-1 激活会促进损伤，但 TREM-1 信号在无菌炎症背景下的组织驻留细胞中的作用仍不甚明了。在这里，我们利用心脏移植模型来研究心脏驻留细胞中Trem1/3的表达如何调节无菌性炎症。在小鼠和人类中，TREM-1在心脏驻留的C-C趋化因子受体2（CCR2）+巨噬细胞中表达。组织驻留的 CCR2+ 巨噬细胞中的 TREM-1/3 信号促进 C-C motif 趋化因子配体 3 (CCL3) 的产生，对心脏移植后中性粒细胞和 CCR2+ 单核细胞的募集至关重要。我们证明，与野生型心脏相比，Trem1/3缺陷型心脏移植后的异体移植存活时间更长。我们发现供体移植物中的 TREM-1/3 信号传导是未来缓解心肌缺血再灌注损伤后炎症的潜在治疗靶点。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.