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Dysregulation of metabolic pathways in circulating natural killer cells isolated from inflammatory bowel disease patients

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Show simple item record Bittencourt, Vanessa Zaiatz Jones, Fiona Tosetto, Miriam Doherty, Glen A. Ryan, Elizabeth J. 2022-01-13T11:51:34Z 2022-01-13T11:51:34Z 2021
dc.description peer-reviewed en_US
dc.description.abstract Background and Aims: Inflammatory bowel diseases [IBD], comprising Crohn’s disease [CD] and ulcerative colitis [UC], are chronic conditions characterized by severe dysregulation of innate and adaptive immunity resulting in the destruction of the intestinal mucosa. Natural killer [NK] cells play a pivotal role in the dynamic interaction between the innate and adaptive immune response. There is an increasing appreciation for the key role immunometabolism plays in the regulation of NK cell function, yet little remains known about the metabolic profile, cytokine secretion, and killing capacity of human NK cells during active IBD. Methods: Peripheral blood mononuclear cells were isolated from peripheral blood of patients with moderate to severely active IBD and healthy controls. NK cells were stained with a combination of cell surface receptors, intracellular cytokines, and proteins and analyzed by flow cytometry. For measurements of NK cell cytotoxicity, the calcein-AM release assay was performed. The metabolic profile was analyzed by an extracellular flux analyzer. Results: NK cells from IBD patients produce large quantities of pro-inflammatory cytokines, IL-17A and TNF-α ex vivo, but have limited killing capability. Furthermore, patient NK cells have reduced mitochondrial mass and oxidative phosphorylation. mTORC1, an important cell and metabolic regulator, demonstrated limited activity in both freshly isolated cells and cytokine-stimulated cells. Conclusions: Our results demonstrate that circulating NK cells of IBD patients have an unbalanced metabolic profile, with faulty mitochondria and reduced capacity to kill. These aberrations in NK cell metabolism may contribute to defective killing and thus the secondary infections and increased risk of cancer observed in IBD patients. en_US
dc.language.iso eng en_US
dc.publisher Oxford University Press en_US
dc.relation.ispartofseries Journal of Crohn's and Colitis;pp.1316–1325
dc.subject NK cell en_US
dc.subject mTORC en_US
dc.title Dysregulation of metabolic pathways in circulating natural killer cells isolated from inflammatory bowel disease patients en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.1093/ecco-jcc/jjab014
dc.contributor.sponsor AbbVie Newman Fellowship in Inflammatory Bowel Disease 2019 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US

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