当前位置:科学网首页 > 小柯机器人 >详情
醋酸盐通过Tip60组蛋白乙酰转移酶复合物激活肠道先天免疫
作者:小柯机器人 发布时间:2021/6/9 15:33:47

美国波士顿儿童医院Paula I. Watnick研究组发现,微生物群来源的醋酸盐通过Tip60组蛋白乙酰转移酶复合物激活肠道先天免疫。2021年6月8日,《免疫》杂志在线发表了这项成果。

研究人员表示,微生物来源的醋酸盐激活中肠前部肠内分泌细胞(EEC)亚群中的IMD(Drosophila immunodeficiency)通路。在这些细胞中,IMD通路共同调节抗菌肽和肠内分泌肽的表达,包括速激肽,这是一种肠道脂质合成的抑制剂。

为了确定醋酸盐是作用于细胞表面模式识别受体还是细胞内靶标,研究人员分析了醋酸盐摄入是否对IMD信号传导至关重要。诱变和RNA干扰表明,推测的单羧酸转运蛋白Tarag对通过膳食醋酸盐增强IMD信号至关重要。干扰EEC中的组蛋白去乙酰化增强了受类固醇激素蜕皮激素调节的基因的转录,包括IMD靶标。组蛋白乙酰转移酶Tip60的表达减少会降低IMD信号并阻止膳食醋酸盐和其他细胞内乙酰辅酶A来源的拯救。因此,微生物来源的醋酸盐诱导肠内分泌细胞内的染色质重塑,进而通过在哺乳动物中保守的Tip60-类固醇激素信号轴共同调节宿主代谢和肠道先天免疫。

附:英文原文

Title: Microbiota-derived acetate activates intestinal innate immunity via the Tip60 histone acetyltransferase complex

Author: Bat-Erdene Jugder, Layla Kamareddine, Paula I. Watnick

Issue&Volume: 2021-06-08

Abstract: Microbe-derived acetate activates the Drosophila immunodeficiency (IMD) pathway in a subset of enteroendocrine cells (EECs) of theanterior midgut. In these cells, the IMD pathway co-regulates expression of antimicrobialand enteroendocrine peptides including tachykinin, a repressor of intestinal lipidsynthesis. To determine whether acetate acts on a cell surface pattern recognitionreceptor or an intracellular target, we asked whether acetate import was essentialfor IMD signaling. Mutagenesis and RNA interference revealed that the putative monocarboxylicacid transporter Tarag was essential for enhancement of IMD signaling by dietary acetate.Interference with histone deacetylation in EECs augmented transcription of genes regulatedby the steroid hormone ecdysone including IMD targets. Reduced expression of the histoneacetyltransferase Tip60 decreased IMD signaling and blocked rescue by dietary acetateand other sources of intracellular acetyl-CoA. Thus, microbe-derived acetate induceschromatin remodeling within enteroendocrine cells, co-regulating host metabolism andintestinal innate immunity via a Tip60-steroid hormone axis that is conserved in mammals.

DOI: 10.1016/j.immuni.2021.05.017

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00223-5

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx