Liver-resident NK cells confer adaptive immunity in skin-contact inflammation

Liver natural killer (NK) cells were recently reported to possess memory-like properties in contact hypersensitivity (CHS) models. However, the phenotype and origin of these "memory" NK cells cannot be distinguished from other NK cell subpopulations. Here, we define the transcriptional, phenotypic, and functional features of liver NK cell subsets and their roles in mediating CHS. Liver NK cells can be divided into two distinct subsets: CD49a(+)DX5(-) and CD49a(-)DX5(+). Substantial transcriptional and phenotypic differences existed between liver CD49a(+)DX5(-) NK cells and other NK cell subsets. CD49a(+)DX5(-) NK cells possessed memory potential and conferred hapten-specific CHS responses upon hapten challenge. Importantly, CD49a(+)DX5(-) NK cells were liver resident and were present in the liver sinusoidal blood, but not the afferent and efferent blood of the liver. Moreover, they appeared to originate from hepatic hematopoietic progenitor/stem cells (HPCs/HSCs) but not from the bone marrow, and maintained their phenotypes in the steady state. Our findings of liver-resident NK cells shed new light on the acquisition of memory-like properties of NK cells.