China University of Science and Technology reveals the heterogeneity of liver resident NK cells

On May 2, 2022, A team led by Professor Tian Zhigang and Professor Peng Hui from the University of Science and Technology of China published a paper entitled "Ly49E separates liver ILC1s into embryo-derived and derived" in the internationally renowned Journal of Experimental Medicine "postnatal subsets with different functions" research paper, which for the first time revealed the heterogeneity of liver-domiciled NK cells (i.e., liver ILC1s), finding that it consists of two cell subpopulations with different origins and functions.

NK cells (natural killer cells), as an important member of innate immunity, are abundant in the liver. In 2013, Professor Tian Zhigang's team reported internationally for the first time that a new subpopulation different from classical NK cells settled in the liver, accounting for about half of the total NK cells in the liver, which was later classified as one of the three inherent lymphocytes, called liver ILC1s (J Clin Invest 2013). The research group subsequently carried out in-depth studies on the development, differentiation and functional characteristics of this group of cells, and made a series of progress (Science 2021; Hepatology 2021;  Immunity 2019;  Nat Commun 2018;  Hepatology 2019;  J Autoimmun 2016), but whether the functional diversity of this group of cells is related to the heterogeneous composition remains an unsolved mystery.

Through single-cell sequencing and flow cytometry, we found that liver ILC1s could be divided into Ly49E+ and Ly49E - groups of cells. Using an inducible lineage tracer mouse model, it was found that Ly49E+ILC1s was mainly produced by embryonic hematopoietic precursors, dominated in the early ontogenetic stage, and could be self-sustained for a long time after birth without dependence on hematopoietic precursors. Ly49e-ilc1s depended on the continuous replenishment of hematopoietic precursor cells, and with the increase of age, this group of cells gradually became the main group of liver ILC1s. In terms of function, Ly49E+ILC1s has more powerful cytotoxicity and can mediate effective antiviral immune response in the neonatal period. Ly49e-ilc1s has stronger immune memory potential and can mediate the immune response to haptens. In this study, we explored the origin and functional heterogeneity of liver ILC1s, and the dynamic changes of its heterogeneous composition with age may be to meet the needs of innate and adaptive immunity at different stages of the body. In addition, the immune defense effect of embryo-derived LY49E-ILC1s on newborn bodies revealed in this study also provides new clues for immunotherapy of neonatal related diseases.

Figure 1 Composition of liver NK cells (Group 1 ILCs)

The research work was supported by the National Natural Science Foundation of China, the Ministry of Science and Technology, and the Chinese Academy of Medical Sciences. Corresponding authors are Professors Zhigang Tian and Hui Peng from the University of Science and Technology of China. Postdoctoral fellow Yawen Chen and special Associate Researcher Xianwei Wang are co-first authors of the paper.

Paper link:https://doi.org/10.1084/jem.20211805

(Ministry of Health and Medicine, Key Laboratory of Natural Immunity and Chronic Diseases, Chinese Academy of Sciences, Department of Scientific Research)