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 5

CD49a is a specific surface marker of liver-resident DX5– NK cells.

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CD49a is a specific surface marker of liver-resident DX5– NK cells. (A...
(A) Expression of CD49a, NKp46, CD51, CD27, CXCR6, and Thy1.2 versus DX5 was analyzed on NK1.1+CD3–CD19– cells or NK1.1+CD3– cells from the indicated organs of WT or CXCR6+/– (for CXCR6 detection) mice. Data are representative of 4 to 6 individual mice. (B) DX5– or DX5+ liver NK (NK1.1+ CD3– CD19–) cells (105) were sorted from CD45.1+ mice and intravenously transferred into sublethally irradiated CD45.2+ B6 mice. Seven days later, NK cells from recipient liver were analyzed for the expression of CD45.1 and CD49a. Data are representative of 2 independent experiments. (C) Expression of CD49a was analyzed on NK cells from unmanipulated BALB/c and Rag1–/– mice. Numbers indicate the percentages of cells expressing CD49a among NKp46+CD3–CD19– (BALB/c) or NK1.1+ (Rag1–/–) cells. Blue lines represent staining of the indicated molecules, and gray-shaded curves represent isotype controls. Data are representative of 4 mice per group. (D) As described in Methods, blood was collected from the unfractionated liver and other indicated sites from WT B6 mice, and then MNCs were isolated. Expression of CD49a versus DX5 was analyzed on NK1.1+CD3–CD19– cells. Plots are representative of at least 5 individual mice. (E) Immunofluorescence histology of frozen sections of mouse liver stained with anti-NKp46 (green), anti-CD31 (blue), anti-CD49a (red), or anti-CD49b (DX5; red). Original magnification, ×250. (F) Histological analysis of Rag1–/– mouse liver stained with anti-CD49a (brown) and NK1.1 (purple). Original magnification, ×320. (E and F) Data are representative of at least 2 independent experiments.