Il13r2 Expression Identifies Tissue-Resident Il-22-Producing Plzf(+) Innate Tcells In The Human Liver

Innate lymphocytes are selectively enriched in the liver where they have important roles in liver immunology. Murine studies have shown that type I NKTcells can promote liver inflammation, whereas type II NKTcells have an anti-inflammatory role. In humans, type II NKTcells were found to accumulate in the gut during inflammation and IL13R2 was proposed as a marker for these cells. In the human liver, less is known about type I and II NKTcells. Here, we studied the phenotype and function of human liver Tcells expressing IL13R2. We found that IL13R2 was expressed by around 1% of liver-resident memory Tcells but not on circulating Tcells. In support of their innate-like T-cell character, the IL13R2(+) Tcells had higher expression of promyelocytic leukaemia zinc finger (PLZF) compared to IL13R2(-) Tcells and possessed the capacity to produce IL-22. However, only a minority of human liver sulfatide-reactive type II NKTcells expressed IL13R2. Collectively, these findings suggest that IL13R2 identifies tissue-resident intrahepatic Tcells with innate characteristics and the capacity to produce IL-22.