Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC, USA.
Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Eur J Immunol. 2018 Aug;48(8):1329-1335. doi: 10.1002/eji.201747334. Epub 2018 May 25.
Innate lymphocytes are selectively enriched in the liver where they have important roles in liver immunology. Murine studies have shown that type I NKT cells can promote liver inflammation, whereas type II NKT cells have an anti-inflammatory role. In humans, type II NKT cells were found to accumulate in the gut during inflammation and IL13Rα2 was proposed as a marker for these cells. In the human liver, less is known about type I and II NKT cells. Here, we studied the phenotype and function of human liver T cells expressing IL13Rα2. We found that IL13Rα2 was expressed by around 1% of liver-resident memory T cells but not on circulating T cells. In support of their innate-like T-cell character, the IL13Rα2 T cells had higher expression of promyelocytic leukaemia zinc finger (PLZF) compared to IL13Rα2 T cells and possessed the capacity to produce IL-22. However, only a minority of human liver sulfatide-reactive type II NKT cells expressed IL13Rα2. Collectively, these findings suggest that IL13Rα2 identifies tissue-resident intrahepatic T cells with innate characteristics and the capacity to produce IL-22.
固有淋巴细胞在肝脏中选择性富集,在肝脏免疫学中具有重要作用。鼠类研究表明,I 型 NKT 细胞可促进肝脏炎症,而 II 型 NKT 细胞则具有抗炎作用。在人类中,发现 II 型 NKT 细胞在炎症期间积聚在肠道中,并且提出了 IL13Rα2 作为这些细胞的标志物。在人类肝脏中,对 I 型和 II 型 NKT 细胞的了解较少。在这里,我们研究了表达 IL13Rα2 的人类肝脏 T 细胞的表型和功能。我们发现,大约 1%的肝驻留记忆 T 细胞表达 IL13Rα2,但循环 T 细胞不表达。为了支持它们的固有样 T 细胞特征,IL13Rα2 T 细胞表达的早幼粒细胞白血病锌指 (PLZF) 高于 IL13Rα2 T 细胞,并且具有产生 IL-22 的能力。然而,只有少数人类肝脏硫脂反应性 II 型 NKT 细胞表达 IL13Rα2。总的来说,这些发现表明,IL13Rα2 鉴定了具有固有特征和产生 IL-22 能力的组织驻留肝内 T 细胞。