Terada Yuriko, Li Wenjun, Amrute Junedh M, Bery Amit I, Liu Charles R, Nunna Venkatrao, Frye Christian Corbin, Dun Hao, Koenig Andrew L, Luehmann Hannah P, Heo Gyu Seong, Owen Macee C, Wein Alexander N, Liu Yongjian, Ritter Jon H, Prabhu Sumanth D, Nava Ruben G, Gelman Andrew E, Cella Marina, Colonna Marco, Lavine Kory J, Kreisel Daniel
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell Rep. 2025 Mar 25;44(3):115380. doi: 10.1016/j.celrep.2025.115380. Epub 2025 Mar 4.
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.
髓系细胞触发受体1（TREM-1）已被证明在感染和无菌性损伤后可放大炎症信号，如Toll样受体信号。虽然先前的研究表明循环免疫细胞中的TREM-1激活会促进损伤，但在无菌性炎症背景下，TREM-1信号在组织驻留细胞中的作用仍知之甚少。在这里，我们使用心脏移植模型来剖析心脏驻留细胞上的Trem1/3表达如何调节无菌性炎症。TREM-1在小鼠和人类的心脏驻留C-C趋化因子受体2（CCR2）巨噬细胞中表达。组织驻留CCR2巨噬细胞中的TREM-1/3信号促进C-C基序趋化因子配体3（CCL3）的产生，并且对于心脏移植后募集中性粒细胞和CCR2单核细胞至关重要。我们证明，与野生型心脏相比，Trem1/3缺陷型心脏移植后同种异体移植物存活时间延长。我们确定供体移植物中的TREM-1/3信号是心肌缺血再灌注损伤后减轻炎症的潜在未来治疗靶点。
