{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:16:38Z","timestamp":1790691398668,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008662","name":"Joachim Herz Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008662","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SO 1402\/1\u20101"],"award-info":[{"award-number":["SO 1402\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The expression of FA metabolism\u2013related 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\u00a0=\u00a031), psoriatic arthritis (n\u00a0=\u00a026), and spondyloarthritis (n\u00a0=\u00a021) patients receiving different therapies (disease\u2010modifying antirheumatic drugs, biologics, and JAK inhibitors) and from healthy controls (n\u00a0=\u00a014). 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The CD8+ T cell gene expression profile of FA metabolism\u2013related 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\u2013related genes. Cell surface expression of the FA transporters FA binding protein 4 (FABP4) and G protein\u2013coupled 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42456-toc-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42456","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T03:29:22Z","timestamp":1674790162000},"page":"1098-1109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Reduction of Proinflammatory Effector Functions Through Remodeling of Fatty Acid Metabolism in\n                    <scp>CD8<\/scp>\n                    + T Cells From Rheumatoid Arthritis Patients"],"prefix":"10.1002","volume":"75","author":[{"given":"Franziska V.","family":"Kraus","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine 5 Hematology Oncology Rheumatology Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Keck","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine 5 Hematology Oncology Rheumatology Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel D.","family":"Klika","sequence":"additional","affiliation":[{"name":"Molecular Structure Analysis German Cancer Research Centre  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Graf","sequence":"additional","affiliation":[{"name":"Nuclear Magnetic Resonance Laboratory Institute of Organic Chemistry, Universit\u00e4t Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui A.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Coimbra Faculty of Sciences and Technology  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanns\u2010Martin","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine 5 Hematology Oncology Rheumatology Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6923-0590","authenticated-orcid":false,"given":"M. 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