Liver-resident NK cells confer adaptive immunity in skin-contact inflammation
Hui Peng, Xiaojun Jiang, Yonglin Chen, Dorothy K. Sojka, Haiming Wei, Xiang Gao, Rui Sun, Wayne M. Yokoyama, Zhigang Tian
Hui Peng, Xiaojun Jiang, Yonglin Chen, Dorothy K. Sojka, Haiming Wei, Xiang Gao, Rui Sun, Wayne M. Yokoyama, Zhigang Tian
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Research Article Immunology

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

Abstract

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.

Authors

Hui Peng, Xiaojun Jiang, Yonglin Chen, Dorothy K. Sojka, Haiming Wei, Xiang Gao, Rui Sun, Wayne M. Yokoyama, Zhigang Tian

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Figure 3

Hepatic DX5– NK cells preferentially traffic to the liver and maintain their phenotypic features after adoptive transfer.

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Hepatic DX5– NK cells preferentially traffic to the liver and maintain t...
(A) Liver MNCs (106) from CD45.1+ mice were adoptively transferred intravenously into sublethally irradiated (IR) CD45.2+ B6 mice. Twenty-four hours after transfer, CD45.1+ NK (NK1.1+CD3–CD19–) cells were analyzed for DX5 expression in recipient liver, spleen, and BM. (B) DX5– or DX5+ liver NK cells (105) were sorted from CD45.1+ mice and intravenously transferred into sublethally irradiated CD45.2+ B6 mice. DX5 expression of donor NK cells before transfer is shown pre- and post-sort. Seven days after transfer, CD45.1+ NK cells were analyzed for DX5 expression in recipient liver and spleen. All data in this figure are representative of 2 independent experiments.