Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/112412
DC Field | Value | Language |
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dc.contributor.author | Kraus, Franziska V | - |
dc.contributor.author | Keck, Simon | - |
dc.contributor.author | Klika, Karel D | - |
dc.contributor.author | Graf, Jürgen | - |
dc.contributor.author | Carvalho, Rui A. | - |
dc.contributor.author | Lorenz, Hanns-Martin | - |
dc.contributor.author | Souto-Carneiro, M Margarida | - |
dc.date.accessioned | 2024-01-31T12:24:32Z | - |
dc.date.available | 2024-01-31T12:24:32Z | - |
dc.date.issued | 2023-07 | - |
dc.identifier.issn | 2326-5191 | pt |
dc.identifier.issn | 2326-5205 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/112412 | - |
dc.description.abstract | Objective. Rheumatoid arthritis (RA) CD8+ T cells maintain their effector proinflammatory phenotype by changing their metabolism toward aerobic glycolysis. However, their massive energy and biosynthesis 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+ T cells to identify potential targets to curb their proinflammatory potential. Methods. The expression of FA metabolism–related genes was analyzed for total CD8+ T cells and CD8+ T cell subsets in the data of RA patients and healthy controls retrieved from the GEO database. Functional assays were performed using peripheral blood CD8+ T cells isolated from RA (n = 31), psoriatic arthritis (n = 26), and spondyloarthritis (n = 21) patients receiving different therapies (disease-modifying antirheumatic drugs, biologics, and JAK inhibitors) and from healthy controls (n = 14). 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. Results. The CD8+ T cell gene expression profile of FA metabolism–related genes was significantly different between untreated RA patients and healthy controls. RA patients who had a good clinical response after 6 months of methotrexate therapy had significantly increased expression of FA metabolism–related genes. Cell surface expression of the FA transporters FA binding protein 4 (FABP4) and G protein–coupled receptor 84 (GPR84) and FA uptake were higher in effector and memory CD8+ T cells from RA patients compared to those from healthy controls. In vitro blockade of FA metabolism significantly impaired CD8+ T cell effector functions. Conclusion. RA CD8+ T cells present an altered FA metabolism, which could provide potential therapeutic targets to control their proinflammatory profile, particularly therapies directed against the transport and oxidation of free FA. | pt |
dc.description.sponsorship | Dr. Kraus’s work was supported by an Add-On Fellowship from the Joachim Herz Foundation. Dr. Lorenz’s work was supported by the Heidelberg Medical School. Dr. Souto-Carneiro’s work was supported by the German Research Foundation (grant SO 1402/1-1) | pt |
dc.language.iso | eng | pt |
dc.publisher | Wiley-Blackwell | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | CD8-Positive T-Lymphocytes | pt |
dc.subject.mesh | T-Lymphocyte Subsets | pt |
dc.subject.mesh | Lipid Metabolism | pt |
dc.subject.mesh | Fatty Acids | pt |
dc.subject.mesh | Arthritis, Rheumatoid | pt |
dc.title | Reduction of Proinflammatory Effector Functions Through Remodeling of Fatty Acid Metabolism in CD8+ T Cells From Rheumatoid Arthritis Patients | pt |
dc.type | article | - |
degois.publication.firstPage | 1098 | pt |
degois.publication.lastPage | 1109 | pt |
degois.publication.issue | 7 | pt |
degois.publication.title | Arthritis and Rheumatology | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1002/art.42456 | pt |
degois.publication.volume | 75 | pt |
dc.date.embargo | 2023-07-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.fulltext | Com Texto completo | - |
item.grantfulltext | open | - |
item.languageiso639-1 | en | - |
item.cerifentitytype | Publications | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0003-1820-0353 | - |
Appears in Collections: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
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File | Description | Size | Format | |
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Arthritis Rheumatology - 2023 - Kraus - Reduction of Proinflammatory Effector Functions Through Remodeling of Fatty Acid.pdf | 1.77 MB | Adobe PDF | View/Open |
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