Liver-resident NK cells confer adaptive immunity in skin-contact inflammation
Hui Peng, … , Wayne M. Yokoyama, Zhigang Tian
Hui Peng, … , Wayne M. Yokoyama, Zhigang Tian
Published March 25, 2013
Citation Information: J Clin Invest. 2013;123(4):1444-1456. https://doi.org/10.1172/JCI66381.
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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 2

Hepatic NK cells with memory capacity remain DX5– during hapten sensitization.

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Hepatic NK cells with memory capacity remain DX5– during hapten sensitiz...
(A) DX5– or DX5+ NK (NK1.1+CD3–CD19–) cells (105) from naive GFP transgenic mice were adoptively transferred into lethally irradiated recipients, which were sensitized with 5% OXA on days 1 and 2. On day 5, liver MNCs from recipients or control irradiated mice that did not receive any cells were adoptively transferred into secondary recipients that were challenged 1 month later. (B) DX5 expression on GFP+ NK cells in the irradiated recipients that received GFP+DX5– (top panel) or GFP+DX5+ (bottom panel) NK cells was analyzed on day 5 before transfer. (C) Ear swelling of secondary recipients described in A was measured after OXA challenge (n = 5 per group). ***P < 0.001, ANOVA. Means ± SEM are shown. Hepatocytes (D) or F4/80+ Kupffer cells (E) in the liver of sensitized (blue) or control (gray shaded) WT mice were respectively isolated by a 2-step collagenase perfusion method, then gated and analyzed for FITC expression; the statistical results show FITC MFI on sensitized (n = 6) or control (n = 2) hepatocytes. *P < 0.05, unpaired Student’s t test. Means ± SEM are shown. (F) FITC+ cells in Rag1–/– mice 24 hours after sensitization of FITC on 2 consecutive days. Rag1–/– mice without sensitization were set as controls. FITC+ cells among liver MNCs from sensitized mice were analyzed for the expression of indicated markers. (B–F) Data are representative of 2 or 3 independent experiments. SSC, side scatter.