近日，美国斯坦福大学医学院教授Xi Yang及其研究组探明了外周TREM1对脑及肠道免疫原的反应，可加重中风的严重程度。 该项研究成果发表在2019年8月出版的《自然—免疫学》上。

研究团队证明，外周CD11b⁺ CD45⁺髓样细胞通过激活髓样细胞表达的触发受体1 (TREM1)，扩大中风损伤，TREM1是促炎先天免疫反应的放大器。中风发生后数小时内，迁移至缺血脑组织中的外周CD11b⁺CD45⁺细胞诱导表达TREM1。从基因上或药物上抑制TREM1，即可通过保护性抗氧化和抗炎机制提高治疗效果。使用放射性标记抗体识别TREM1的正电子断层扫描成像结果显示TREM1在脾脏和肠道内均表达升高。在肠道粘膜固有层中，去甲肾上腺素依赖性肠道通透性增加会诱导了炎症性Ly6C⁺ MHCII⁺巨噬细胞上TREM1的表达，进一步增加上皮细胞通透性，并促进细菌易位穿过肠道屏障。因此，中风后，外周TREM1的诱发，能够放大对脑源性和肠源性免疫原性成分的促炎症反应。总之，通过靶向这个特定的先天免疫途径可减少大脑损伤。

据悉，中风是一个多相过程，在该过程中最初发生的是脑缺血，继之而来的是针对缺血性脑成分产生的免疫反应引起的继发性损伤。

附：英文原文

Title: Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity

Author: Qingkun Liu, Emily M. Johnson, Rachel K. Lam, Qian Wang, Hong Bo Ye, Edward N. Wilson, Paras S. Minhas, Ling Liu, Michelle S. Swarovski, Stephanie Tran, Jing Wang, Swapnil S. Mehta, Xi Yang

Issue&Volume:Volume 20 Issue 8

Abstract: Stroke is a multiphasic process in which initial cerebral ischemia is followed by secondary injury from immune responses to ischemic brain components. Here we demonstrate that peripheral CD11b+CD45+ myeloid cells magnify stroke injury via activation of triggering receptor expressed on myeloid cells 1 (TREM1), an amplifier of proinflammatory innate immune responses. TREM1 was induced within hours after stroke peripherally in CD11b+CD45+ cells trafficking to ischemic brain. TREM1 inhibition genetically or pharmacologically improved outcome via protective antioxidant and anti-inflammatory mechanisms. Positron electron tomography imaging using radiolabeled antibody recognizing TREM1 revealed elevated TREM1 expression in spleen and, unexpectedly, in intestine. In the lamina propria, noradrenergic-dependent increases in gut permeability induced TREM1 on inflammatory Ly6C+MHCII+ macrophages, further increasing epithelial permeability and facilitating bacterial translocation across the gut barrier. Thus, following stroke, peripheral TREM1 induction amplifies proinflammatory responses to both brain-derived and intestinal-derived immunogenic components. Critically, targeting this specific innate immune pathway reduces cerebral injury.

DOI: 10.1038/s41590-019-0421-2

Source:https://www.nature.com/articles/s41590-019-0421-2