{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T22:36:53Z","timestamp":1792363013212,"version":"4.4.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Studies suggest that immune checkpoints play a role in accelerating the formation of atherosclerosis. We aimed to assess the expression of soluble and membrane-bound immune checkpoints in patients with peripheral artery disease (PAD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The levels of 14 soluble immune checkpoints were assessed in blood plasma of PAD patients (n= 37) and healthy controls (HCs, n=39) by Multiplex protein assay. The surface expression of immune checkpoints on peripheral blood immune cells was determined by flow cytometry. Cytokine production capacity was measured by flow cytometry in TIM-3+ T cells to determine immune exhaustion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Soluble levels of PD-L2 were decreased in female PAD patients, whereas soluble levels of TIM-3 showed a trend towards an increased concentration in female PAD patients. PD-L2+ frequencies were higher within all monocyte subsets in PAD patients. CD4+ T cells from PAD patients had increased frequencies of TIM-3+ cells, showing little overlap with other immune exhaustion markers. TIM-3+ CD4+ T cells from both PAD patients and HCs, had a low capacity to produce pro-inflammatory cytokines, but a higher capacity to produce IL-10 compared to TIM-3- CD4+ T cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PAD patients show differences in the expression of membrane-bound and soluble immune checkpoints. Some of these differences might be caused by prolonged immune activation, although immune exhaustion markers did not always overlap.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1568431","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T04:10:26Z","timestamp":1753071026000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Patients with peripheral artery disease demonstrate altered expression of soluble and membrane-bound immune checkpoints"],"prefix":"10.3389","volume":"16","author":[{"given":"Rosanne 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