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| Home > Publications database > Reduction of pro-inflammatory effector functions through remodeling of fatty acid metabolism in CD8+ T-cells from rheumatoid arthritis patients. |
| Home > Publications database > Reduction of pro-inflammatory effector functions through remodeling of fatty acid metabolism in CD8+ T-cells from rheumatoid arthritis patients. |
| Journal Article | DKFZ-2023-00233 |
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2023
Wiley
Hoboken, NJ
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Please use a persistent id in citations: doi:10.1002/art.42456
Abstract: Rheumatoid arthritis (RA) CD8+ T-cells (CD8) maintain their effector pro-inflammatory phenotype by changing their metabolism towards aerobic glycolysis. However, their massive energetic and biosynthetic needs may require additional substrates other than glucose. Since systemic alterations in lipid metabolism have been reported in RA patients, we explored the role of fatty acid (FA) metabolism in CD8 to identify potential targets to curb their pro-inflammatory potential.The expression of FA metabolism-related genes was analyzed for total and CD8-subsets in the data of RA patients and healthy controls retrieved from the gene expression omnibus database. Functional assays were performed on peripheral-blood CD8 isolated from RA (n=31), PsA (n=26), and SpA (n=21) patients under different therapies (DMARD, biologicals, and JAK inhibitors) and controls (n=13). We quantified the expression of FA transporters, lipid uptake, intracellular FA content, cytokine production, activation, proliferation, and capacity to inhibit tumor cell growth, either with or without FA metabolism inhibitors.The CD8 gene expression profile of FA metabolism-related genes was significantly different between untreated RA patients and controls. RA patients with a good clinical response after 6 months MTX therapy significantly increased the expression of FA metabolism-related genes. Cell-surface expression of FA transporters FABP4 and GPR84 and FA uptake was higher in effector and memory CD8 of RA patients than for controls. In vitro blockade of FA metabolism significantly impaired CD8 effector functions.RA CD8 present an altered FA metabolism which can provide potential therapeutic targets to control the pro-inflammatory profile. Particularly, therapies directed against the transport and oxidation of free FA.
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