The obese liver environment mediates conversion of NK cells to a less cytotoxic ILC1-like phenotype
| Autor: | Male, Ronjon Chakraverty, Simone Dertschnig, Cuff Ao, Francesca Sillito, Andrew M. Hall, Tu Vinh Luong |
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| Přispěvatelé: | Wellcome Trust |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
obesity HOMEOSTASIS immunometabolism NK cells ILC1 DISEASE Mice NATURAL-KILLER-CELLS 0302 clinical medicine PROGRAMS Non-alcoholic Fatty Liver Disease Immunology and Allergy Cytotoxic T cell FIBROSIS Cytotoxicity Original Research Mice Knockout biology Chemistry Fatty liver T-BET Killer Cells Natural Liver 1107 Immunology Female medicine.symptom Life Sciences & Biomedicine lcsh:Immunologic diseases. Allergy Immunology Inflammation 03 medical and health sciences MATERNAL OBESITY TGFβ INFLAMMATION Antigens CD TGF beta NAFLD TGF beta signaling pathway medicine Animals Humans PROMOTE Science & Technology DELETION medicine.disease 030104 developmental biology Perforin Cancer cell biology.protein Cancer research lcsh:RC581-607 Homeostasis 030215 immunology |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 10 (2019) |
| Popis: | The liver contains both NK cells and their less cytotoxic relatives, ILC1. Here, we investigate the role of NK cells and ILC1 in the obesity-associated condition, non-alcoholic fatty liver disease (NAFLD). In the livers of mice suffering from NAFLD, NK cells are less able to degranulate, express lower levels of perforin and are less able to kill cancerous target cells than those from healthy animals. This is associated with a decreased ability to kill cancer cells in vivo. On the other hand, we find that perforin-deficient mice suffer from less severe NAFLD, suggesting that this reduction in NK cell cytotoxicity may be protective in the obese liver, albeit at the cost of increased susceptibility to cancer. The decrease in cytotoxicity is associated with a shift towards a transcriptional profile characteristic of ILC1, increased expression of the ILC1-associated proteins CD200R1 and CD49a, and an altered metabolic profile mimicking that of ILC1. We show that the conversion of NK cells to this less cytotoxic phenotype is at least partially mediated by TGFβ, which is expressed at high levels in the obese liver. Finally, we show that reduced cytotoxicity is also a feature of NK cells in the livers of human NAFLD patients. |
| Databáze: | OpenAIRE |
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