Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY, United States.
Department of Surgery, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, United States.
Front Immunol. 2022 Jun 15;13:907387. doi: 10.3389/fimmu.2022.907387. eCollection 2022.
The triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor, which can be upregulated in inflammatory diseases as an amplifier of immune responses. Once activated, TREM-1 induces the production and release of pro-inflammatory cytokines and chemokines, in addition to increasing its own expression and circulating levels of the cleaved soluble extracellular portion of TREM-1 (sTREM-1). This amplification of the inflammatory response by TREM-1 has now been considered as a critical contributor to the dysregulated immune responses in sepsis. Studies have shown that in septic patients there is an elevated expression of TREM-1 on immune cells and increased circulating levels of sTREM-1, associated with increased mortality. As a result, a considerable effort has been made towards identifying endogenous ligands of TREM-1 and developing TREM-1 inhibitory peptides to attenuate the exacerbated inflammatory response in sepsis. TREM-1 modulation has proven a promising strategy for the development of therapeutic agents to treat sepsis. Therefore, this review encompasses the ligands investigated as activators of TREM-1 thus far and highlights the development and efficacy of novel inhibitors for the treatment of sepsis and septic shock.
髓系细胞表达的触发受体-1（TREM-1）是一种模式识别受体，在炎症性疾病中可被上调，作为免疫反应的放大器。一旦被激活，TREM-1 可诱导促炎细胞因子和趋化因子的产生和释放，除了增加其自身的表达和循环水平的 TREM-1 的切割可溶性细胞外部分（sTREM-1）。TREM-1 对炎症反应的这种放大作用现在被认为是脓毒症中失调的免疫反应的关键因素。研究表明，在脓毒症患者中，免疫细胞上 TREM-1 的表达升高，循环中 sTREM-1 的水平升高，与死亡率增加有关。因此，人们做出了相当大的努力来识别 TREM-1 的内源性配体，并开发 TREM-1 抑制肽来减轻脓毒症中的炎症反应过度。TREM-1 调节已被证明是治疗脓毒症的治疗药物开发的有前途的策略。因此，本综述包括迄今为止作为 TREM-1 激活剂研究的配体，并强调了新型抑制剂治疗脓毒症和感染性休克的开发和疗效。
