Single-cell RNA sequencing identifies a population of human liver-type ILC1s

Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of liver-typeILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s are CD49a+CD94+CD200R1+, express the tran-scription factor T-BET, and do not express the activating receptor NKp80 or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-g, TNF-a, and GM-CSF; however, liver -type ILC1s also produce IL-2 and lack perforin and granzyme-B. Liver-type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-b1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a pop-ulation of human cross-tissue ILC1s.

Automated summary

We identified a distinct population of liver-type ILC1s with unique transcriptional, phenotypic, and functional features, different from other known ILC1 subsets. These liver-type ILC1s express CD49a+CD94+CD200R1+ and the transcription factor T-BET, but not the activating receptor NKp80 or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-g, TNF-a, and GM-CSF, but they also produce IL-2 and lack perforin and granzyme-B. These cells can be expanded in cirrhotic liver tissues and can be generated in vitro from blood-derived ILC precursors in the presence of TGF-b1 and liver sinusoidal endothelial cells. Cells with similar characteristics can also be found in tonsil and intestinal tissues. In conclusion, our study identifies and classifies a population of human cross-tissue ILC1s.