美国哥伦比亚大学Nicholas Arpaia研究团队发现，调节性T细胞产生的双调蛋白促进非酒精性脂肪性肝炎患者的肝纤维化和胰岛素抵抗。2024年2月2日，国际知名学术期刊《免疫》在线发表了这一成果。

研究人员揭示了调节性 T（Treg）细胞在非酒精性脂肪性肝炎（NASH，一种慢性肝损伤）中的功能。在患有NASH的小鼠和人类肝脏中富集了产生双调蛋白（Areg）的Treg细胞。在Treg细胞中缺失Areg（而非在骨髓细胞中），可减少NASH诱发的肝纤维化。慢性肝损伤诱导了与Treg细胞活化相关的转录变化。从机制上讲，Treg细胞衍生的Areg通过表皮生长因子受体（EGFR）信号激活了肝星状细胞中的促纤维化转录程序。

删除Treg细胞中的Areg可保护小鼠免受NASH依赖性葡萄糖耐受不良的影响，这种不良也依赖于肝星状细胞上的EGFR信号转导。Treg细胞中的Areg通过肝细胞检测肝星状细胞衍生的白细胞介素-6促进肝细胞葡萄糖生成。这些研究结果揭示了Treg细胞介导的组织修复功能在慢性肝病中的不良作用，并将肝损伤与NASH依赖性糖耐量减低联系起来。

据了解，Treg细胞产生的Areg可促进急性组织损伤后的修复。

附：英文原文

Title: Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis

Author: Thomas M. Savage, Katherine T. Fortson, Kenia de los Santos-Alexis, Angelica Oliveras-Alsina, Mathieu Rouanne, Sarah S. Rae, Jennifer R. Gamarra, Hani Shayya, Adam Kornberg, Renzo Cavero, Fangda Li, Arnold Han, Rebecca A. Haeusler, Julien Adam, Robert F. Schwabe, Nicholas Arpaia

Issue&Volume: 2024-02-02

Abstract: Production of amphiregulin (Areg) by regulatory T (Treg) cells promotes repair afteracute tissue injury. Here, we examined the function of Treg cells in non-alcoholicsteatohepatitis (NASH), a setting of chronic liver injury. Areg-producing Treg cellswere enriched in the livers of mice and humans with NASH. Deletion of Areg in Treg cells, but not in myeloid cells, reduced NASH-induced liver fibrosis. Chronicliver damage induced transcriptional changes associated with Treg cell activation.Mechanistically, Treg cell-derived Areg activated pro-fibrotic transcriptional programsin hepatic stellate cells via epidermal growth factor receptor (EGFR) signaling. Deletionof Areg in Treg cells protected mice from NASH-dependent glucose intolerance, which alsowas dependent on EGFR signaling on hepatic stellate cells. Areg from Treg cells promotedhepatocyte gluconeogenesis through hepatocyte detection of hepatic stellate cell-derivedinterleukin-6. Our findings reveal a maladaptive role for Treg cell-mediated tissuerepair functions in chronic liver disease and link liver damage to NASH-dependentglucose intolerance.

DOI: 10.1016/j.immuni.2024.01.009

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00034-7