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Inflammation Research

Erschienen in:

10.02.2020 | Original Research Paper

NKp46+ lamina propria natural killer cells undergo metabolic reprogramming in a mouse experimental colitis model

verfasst von: Hongjian Zhou, Xingwang Xie, Bin Jiang, Chao Ke

Erschienen in: Inflammation Research | Ausgabe 4/2020

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Abstract

Objective

Both innate and adaptive immune system play important roles in the onset and progression of inflammatory bowel diseases (IBDs). However, the significance of natural killer (NK) cells for IBDs remains unclear. To understand the biology of colonic lamina propria natural killer (LPNK) cells in IBDs, we characterized LPNK cell metabolism in a murine acute colitis model.

Methods

C57BL/6J mice were fed with 3% dextran sulfate sodium to establish the acute colitis model. Colonic LPNK cells were isolated from mice through flow cytometry. The expression of metabolic genes in LPNK cells was analyzed by transcriptome sequencing and quantitative RT-PCR. Glucose uptake, Seahorse assay, and ATP assay were conducted to assess the metabolic status of LPNK cells. Phos-flow assay was performed to evaluate cell signaling pathways in LPNK cells. In vitro stimulation and cytotoxicity assay were conducted to measure the function of LPNK cells.

Results

In acute colitis, LPNK cells upregulated the expression of genes related to glycolysis and oxidative phosphorylation (oxphos), and enhanced glucose uptake capability. Intracellular ATP production, glycolysis and oxphos in LPNK cells were also promoted in acute colitis. mTORC1 signaling was essential for the metabolic reprogramming in LPNK cells in acute colitis. Although LPNK cells of diseased mice exhibited equivalent cytokine profile to normal LPNK cells upon stimulation with phorbol ester or IL-2, LPNK cells of diseased mice were more cytotoxic to target cells than normal LPNK cells.

Conclusions

LPNK cells undergo metabolic reprogramming which might be a response to upcoming microbial infection in acute colitis.

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Titel: NKp46+ lamina propria natural killer cells undergo metabolic reprogramming in a mouse experimental colitis model
verfasst von: Hongjian Zhou
Xingwang Xie
Bin Jiang
Chao Ke
Publikationsdatum: 10.02.2020
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 4/2020
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-020-01324-2

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NKp46+ lamina propria natural killer cells undergo metabolic reprogramming in a mouse experimental colitis model

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Objective

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