{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T18:46:20Z","timestamp":1785005180381,"version":"3.55.0"},"reference-count":73,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Nierstichting","doi-asserted-by":"publisher","award":["CP 16.03"],"award-info":[{"award-number":["CP 16.03"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Levamisole (LMS) is a small molecule used in the treatment of idiopathic nephrotic syndrome (INS). The pathogenesis of INS remains unknown, but evidence points toward an immunological basis of the disease. Recently, LMS has been shown to increase the relapse\u2010free survival in INS patients. While LMS has been hypothesized to exert an immunomodulatory effect, its mechanism of action remains unknown. Here, we show that LMS decreased activation and proliferation of human T cells. T\u2010cell activation\u2010associated cytokines such as IL\u20102, TNF\u2010\u03b1, and IFN\u2010\u03b3 were reduced upon LMS treatment, whereas IL\u20104 and IL\u201013 were increased. Gene expression profiling confirmed that the suppressive effects of LMS as genes involved in cell cycle progression were downregulated. Furthermore, genes associated with p53 activation were upregulated by LMS. In agreement, LMS treatment resulted in p53 phosphorylation and increased expression of the p53 target gene\n                    <jats:italic>FAS<\/jats:italic>\n                    . Accordingly, LMS sensitized activated T cells for Fas\u2010mediated apoptosis. LMS treatment resulted in a mid\u2010S phase cell cycle arrest accompanied by \u03b3H2AX\u2010foci formation and phosphorylation of CHK1. Our findings indicate that LMS acts as an immunosuppressive drug that directly affects the activation and proliferation of human T cells by induction of DNA damage and the activation of a p53\u2010dependent DNA damage response.\n                  <\/jats:p>","DOI":"10.1002\/eji.202350562","type":"journal-article","created":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T17:54:35Z","timestamp":1692467675000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Levamisole suppresses activation and proliferation of human T cells by the induction of a p53\u2010dependent DNA damage response"],"prefix":"10.1002","volume":"53","author":[{"given":"Gerarda H.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Pathology Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floor","family":"Veltkamp","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Pediatric Nephrology Emma Children's Hospital Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirte","family":"Scheper","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron A.","family":"Hoebe","sequence":"additional","affiliation":[{"name":"Department of Medical Biology Amsterdam UMC and Cancer Center Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nike","family":"Claessen","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loes","family":"Butter","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia H.M.","family":"Bouts","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology Emma Children's Hospital Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Florquin","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen E. 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