In a study published in Journal of Experimental Medicine, a research team led by Prof. TIAN Zhigang and Prof. PENG Hui from the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences, for the first time revealed the heterogeneity of liver-resident natural killer (NK) cells, namely ILC1s, and found that ILC1s could be dissected into two subpopulations with distinct origins and functions. NK cells, as a significant part of the innate immune system, are enriched in livers. In previous studies, Prof. TIAN identified that the liver ILC1s displayed different characteristics from conventional NK cells. Accounting for roughly half of the NK cells in livers, the new subset was included as one of the three innate lymphocyte types. Prof. TIAN’s team further investigated the development, differentiation and functional properties of ILC1s. However, the relationship between the functional diversity and heterogeneous composition of the cells remains to be unveiled.
By utilizing the single-cell sequencing method and flow cytometric analysis, the researchers demonstrated that liver ILC1s could be classified into Ly49E+ and Ly49E- populations.
The inducible mouse model indicated that Ly49E+ ILC1s were mainly produced by embryonic hematopoietic precursors, which predominated at the early stage of henogenesis and could maintain self-sustaining for a long time after birth. However, Ly49E- ILC1s still relied on hematopoietic precursor cells even after birth and gradually emerged as the dominant population in livers with age. Moreover, possessing stronger cytotoxicity, Ly49E+ ILC1s could mediate effective antiviral immune response in the neonatal period, while Ly49E- ILC1s, with stronger immune memory potential, could mediate the body’s immune memory response to the hapten.
This study showed that the heterogeneous composition of liver ILC1s varied with age to accommodate the needs for innate and adaptive immune at different stages of the body. It also revealed that the embryo-derived Ly49E- ILC1s provided immune defense for the newborns, which shed new light on immunotherapy of neonatal diseases.
