美国华盛顿大学医学院Marco Colonna研究组发现抑制芳烃受体（AHR）可防止肠上皮内淋巴细胞（IEL）的氧化应激和铁死亡。相关论文于2023年2月16日发表于国际顶尖学术期刊《免疫》杂志上。

他们表明AHR抑制子（AHRR）对于维持IEL至关重要。AHRR缺乏以细胞内在的方式降低了IEL代表。单细胞RNA测序揭示了Ahrr−/−IEL中的氧化应激谱。AHRR 缺乏释放了AHR 诱导的CYP1A1 表达，CYP1A1是一种产生活性氧的单加氧酶，增加了Ahrr−/− IEL中的氧化还原失衡、脂质过氧化和铁死亡。

膳食补充硒或维生素E以恢复氧化还原稳态拯救了Ahrr−/− IEL。Ahrr−/−小鼠中IEL的缺失导致对艰难梭菌感染和葡聚糖硫酸钠诱导的结肠炎的易感性。炎症性肠病患者的发炎组织表现出可能导致疾病的Ahrr表达减少。他们的结论是，必须严格调节AHR信号传导，以防止IEL的氧化应激和铁死亡，并保留肠道免疫反应。

研究人员表示，AHR是一种配体激活的转录因子，可增强肠道免疫反应。AHR诱导自身的负调节子AHRR。

附：英文原文

Title: Repression of the aryl-hydrocarbon receptor prevents oxidative stress and ferroptosis of intestinal intraepithelial lymphocytes

Author: Santosh K. Panda, Vincent Peng, Raki Sudan, Alina Ulezko Antonova, Blanda Di Luccia, Takahiro E. Ohara, Jose Luis Fachi, Gary E. Grajales-Reyes, Natalia Jaeger, Tihana Trsan, Susan Gilfillan, Marina Cella, Marco Colonna

Issue&Volume: 2023-02-16

Abstract: The aryl-hydrocarbon receptor (AHR) is a ligand-activated transcription factor thatbuoys intestinal immune responses. AHR induces its own negative regulator, the AHRrepressor (AHRR). Here, we show that AHRR is vital to sustaining intestinal intraepitheliallymphocytes (IELs). AHRR deficiency reduced IEL representation in a cell-intrinsicfashion. Single-cell RNA sequencing revealed an oxidative stress profile in Ahrr/ IELs. AHRR deficiency unleashed AHR-induced expression of CYP1A1, a monooxygenasethat generates reactive oxygen species, increasing redox imbalance, lipid peroxidation,and ferroptosis in Ahrr/ IELs. Dietary supplementation with selenium or vitamin E to restore redox homeostasisrescued Ahrr/ IELs. Loss of IELs in Ahrr/ mice caused susceptibility to Clostridium difficile infection and dextran sodium-sulfate-induced colitis. Inflamed tissue of inflammatorybowel disease patients showed reduced Ahrr expression that may contribute to disease. We conclude that AHR signaling must betightly regulated to prevent oxidative stress and ferroptosis of IELs and to preserveintestinal immune responses.

DOI: 10.1016/j.immuni.2023.01.023

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00035-3