中国科学院脑科学与智能技术卓越创新中心周嘉伟等研究人员合作发现，多发性硬化症小鼠模型中的肠上皮多巴胺受体信号驱动性别特异性疾病恶化。相关论文于2023年11月21日在线发表在《免疫》杂志上。

研究人员发现肠上皮多巴胺D2受体（IEC DRD2）促进了多发性硬化症动物模型的性别特异性疾病进展。肠上皮细胞中选择性缺乏Drd2的雌性小鼠显示出中枢神经系统（CNS）炎症反应减弱，疾病进展减缓。与此相反，过表达或通过苯乙胺给药激活IEC DRD2会加重疾病的严重程度。与此同时，溶菌酶的表达和肠道微生物群的组成也发生了改变，包括乳酸杆菌的数量减少。此外，用乳酸杆菌的代谢产物N-乙酰赖氨酸治疗可抑制小胶质细胞活化和神经变性。总之，这项研究表明，IEC DRD2亢进会影响肠道微生物的丰度，并以雌性偏向的方式增加对CNS自身免疫性疾病的易感性，这为未来针对不同性别干预中枢神经系统自身免疫性疾病开辟了道路。

据了解，虽然肠道微生物群可影响CNS自身免疫性疾病，但肠道上皮对中枢神经系统自身免疫的贡献还不太清楚。

附：英文原文

Title: Intestinal epithelial dopamine receptor signaling drives sex-specific disease exacerbation in a mouse model of multiple sclerosis

Author: Hai-rong Peng, Jia-Qian Qiu, Qin-ming Zhou, Yu-kai Zhang, Qiao-yu Chen, Yan-qing Yin, Wen Su, Shui Yu, Ya-ting Wang, Yuping Cai, Ming-na Gu, Hao-hao Zhang, Qing-qing Sun, Gang Hu, Yi-wen Wu, Jun Liu, Sheng Chen, Zheng-Jiang Zhu, Xin-yang Song, Jia-wei Zhou

Issue&Volume: 2023-11-21

Abstract: Although the gut microbiota can influence central nervous system (CNS) autoimmunediseases, the contribution of the intestinal epithelium to CNS autoimmunity is lessclear. Here, we showed that intestinal epithelial dopamine D2 receptors (IEC DRD2)promoted sex-specific disease progression in an animal model of multiple sclerosis.Female mice lacking Drd2 selectively in intestinal epithelial cells showed a blunted inflammatory responsein the CNS and reduced disease progression. In contrast, overexpression or activationof IEC DRD2 by phenylethylamine administration exacerbated disease severity. Thiswas accompanied by altered lysozyme expression and gut microbiota composition, includingreduced abundance of Lactobacillus species. Furthermore, treatment with N2-acetyl-L-lysine, a metabolite derived fromLactobacillus, suppressed microglial activation and neurodegeneration. Taken together, our studyindicates that IEC DRD2 hyperactivity impacts gut microbial abundances and increasessusceptibility to CNS autoimmune diseases in a female-biased manner, opening up futureavenues for sex-specific interventions of CNS autoimmune diseases.

DOI: 10.1016/j.immuni.2023.10.016

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00456-9