Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56100 Pisa, Italy.
I.R.C.C.S Neuromed, Via Atinense 18, 86077 Pozzilli, Italy.
Cells. 2019 Sep 21;8(10):1124. doi: 10.3390/cells8101124.
Alterations in Triggering Receptors Expressed on Myeloid cells (TREM-1/2) are bound to a variety of infectious, sterile inflammatory, and degenerative conditions, ranging from inflammatory bowel disease (IBD) to neurodegenerative disorders. TREMs are emerging as key players in pivotal mechanisms often concurring in IBD and neurodegeneration, namely microbiota dysbiosis, leaky gut, and inflammation. In conditions of dysbiosis, compounds released by intestinal bacteria activate TREMs on macrophages, leading to an exuberant pro-inflammatory reaction up to damage in the gut barrier. In turn, TREM-positive activated macrophages along with inflammatory mediators may reach the brain through the blood, glymphatic system, circumventricular organs, or the vagus nerve via the microbiota-gut-brain axis. This leads to a systemic inflammatory response which, in turn, impairs the blood-brain barrier, while promoting further TREM-dependent neuroinflammation and, ultimately, neural injury. Nonetheless, controversial results still exist on the role of TREM-2 compared with TREM-1, depending on disease specificity, stage, and degree of inflammation. Therefore, the present review aimed to provide an update on the role of TREMs in the pathophysiology of IBD and neurodegeneration. The evidence here discussed the highlights of the potential role of TREMs, especially TREM-1, in bridging inflammatory processes in intestinal and neurodegenerative disorders.
髓系细胞表达的触发受体（TREM-1/2）的改变与多种感染、无菌性炎症和退行性疾病有关，范围从炎症性肠病（IBD）到神经退行性疾病。TREMs 作为关键分子出现在 IBD 和神经退行性疾病中常见的关键机制中，即微生物失调、肠道渗漏和炎症。在失调的情况下，肠道细菌释放的化合物会激活巨噬细胞上的 TREMs，导致过度的促炎反应，直至肠道屏障受损。反过来，TREM 阳性激活的巨噬细胞和炎症介质可能通过血液、神经胶质淋巴系统、室周器官或迷走神经通过微生物群-肠道-大脑轴到达大脑。这导致全身炎症反应，反过来又损害血脑屏障，同时促进进一步的 TREM 依赖性神经炎症，最终导致神经损伤。然而，TREM-2 与 TREM-1 相比的作用仍存在争议，这取决于疾病的特异性、阶段和炎症程度。因此，本综述旨在提供关于 TREMs 在 IBD 和神经退行性变发病机制中的作用的最新信息。这里讨论的证据强调了 TREMs，特别是 TREM-1，在桥接肠道和神经退行性疾病中的炎症过程中的潜在作用。
