Hongjian Zhou1, Xingwang Xie1, Bin Jiang1, Chao Ke2. 1. Department of Gastrointestinal, Hernia and Abdominal Wall Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Hubei Province, 241 Pengliuyang Road, Wuchang District, Wuhan, 430060, China. 2. Department of Gastrointestinal, Hernia and Abdominal Wall Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Hubei Province, 241 Pengliuyang Road, Wuchang District, Wuhan, 430060, China. Kechao771106@hotmail.com.
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.
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 murineacute 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.
Authors: Aline Van Acker; Konrad Gronke; Aindrila Biswas; Liesbet Martens; Yvan Saeys; Jessica Filtjens; Sylvie Taveirne; Els Van Ammel; Tessa Kerre; Patrick Matthys; Tom Taghon; Bart Vandekerckhove; Jean Plum; Ildiko Rita Dunay; Andreas Diefenbach; Georges Leclercq Journal: Cell Rep Date: 2017-05-16 Impact factor: 9.423
Authors: Sébastien Viel; Antoine Marçais; Fernando Souza-Fonseca Guimaraes; Roisin Loftus; Jessica Rabilloud; Morgan Grau; Sophie Degouve; Sophia Djebali; Amélien Sanlaville; Emily Charrier; Jacques Bienvenu; Julien C Marie; Christophe Caux; Jacqueline Marvel; Liam Town; Nicholas D Huntington; Laurent Bartholin; David Finlay; Mark J Smyth; Thierry Walzer Journal: Sci Signal Date: 2016-02-16 Impact factor: 8.192