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 8

The liver retains HPCs capable of generating CD49a+DX5– NK cells.

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The liver retains HPCs capable of generating CD49a+DX5– NK cells. (A) ...
(A) Lethally irradiated CD45.2+ B6 mice that received 2 × 106 BM cells from CD45.1+ B6 mice were analyzed for the expression of DX5 on hepatic CD45.1+ NK (NK1.1+CD3–CD19–) cells. Means ± SEM are shown (n = 3 for each time point). (B) Survival of lethally irradiated B6 mice that received 3 × 106 BM cells (BMT), liver MNCs (LT), or splenocytes (ST). Lethally irradiated mice without transplantation were set as the control group. Means ± SEM are shown (n = 5 per group). (C and D) Lethally irradiated CD45.2+ B6 mice received 106 CD45.1+CD45.2+ (DP) BM cells mixed with 106 CD45.1+CD45.2– (SP) liver MNCs. One month after transfer, DP and SP cells in the recipient livers were respectively gated to analyze the expression of DX5 on NK cells. Means ± SEM are shown (n = 3 per group). (E) BM cells (2 × 106) from Nfil3–/– mice mixed with 105 hepatic NK1.1–CD3–CD19– cells from CD45.1+ B6 mice were transferred into lethally irradiated CD45.2+ B6 mice. One month after transfer, CD45.1+ NK cells in the recipient livers were analyzed for the expression of DX5 and CD49a. All data are representative of 2 independent experiments.