{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:43:04Z","timestamp":1791916984440,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870098"],"award-info":[{"award-number":["81870098"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200135"],"award-info":[{"award-number":["82200135"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical & Translational Med"],"published-print":{"date-parts":[[2023,7]]},"abstract":"Background<\/jats:title>The first\u2010line therapy is effective for the treatment of primary immune thrombocytopenia (ITP); however, maintaining the long\u2010term responses remains challenging. Low\u2010dose decitabine (DAC) has been adopted to treat refractory ITP, while its role in macrophage polarization has not been fully understood. We aimed to investigate the mechanistic role of DAC in M2 macrophage polarization and evaluated its therapeutic effect in ITP.<\/jats:p><\/jats:sec>Methods<\/jats:title>The M2 monocytes were identified by flow cytometry from peripheral blood mononuclear cells in healthy controls (HCs) and ITP patients. The expression of PPAR\u03b3, Arg\u20101, DNMT3b and NLRP3, together with IL\u201010 plasma levels was measured to examine its function. Bisulfite\u2010sequencing PCR was used to evaluate the methylation status of PPAR\u03b3 promoter, and the binding affinity of KLF4 was measured by Cut&Tag. A sh\u2010PPAR\u03b3 THP\u20101 cell line was created to verify if low\u2010dose DAC\u2010modulated M2 macrophage polarization was PPAR\u03b3\u2010dependent. The passive ITP models were used to investigate the therapeutic effects of low\u2010dose DAC and its role in modulating polarization and immunomodulatory function of macrophages. NLRP3 inflammasome and reactive oxygen species were also tested to understand the downstream of PPAR\u03b3.<\/jats:p><\/jats:sec>Results<\/jats:title>The M2 monocytes with impaired immunoregulation were observed in ITP. After high\u2010dose dexamethasone (HD\u2010DXM) treatment, M2 monocytes increased significantly with the elevated expression of PPAR\u03b3, Arg\u20101 and IL\u201010 in CR patients. Low\u2010dose DAC promoted M2 macrophage polarization in a PPAR\u03b3\u2010dependent way via demethylating the promoter of PPAR\u03b3, especially the KLF4 binding sites. Low\u2010dose DAC alleviated ITP mice by restoring the M1\/M2 balance and fine\u2010tuning immunomodulatory function of macrophages. The downstream of the PPAR\u03b3 modulation of M2 macrophage polarization might physiologically antagonize NLRP3 inflammasome.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Low\u2010dose DAC promoted M2 macrophage polarization due to the demethylation within the promoter of PPAR\u03b3, thus enhanced the KLF4 binding affinity in ITP.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1344","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T03:50:23Z","timestamp":1690257023000},"source":"Crossref","is-referenced-by-count":37,"title":["Low\u2010dose decitabine promotes M2 macrophage polarization in patients with primary immune thrombocytopenia via enhancing KLF4 binding to PPAR\u03b3 promoter"],"prefix":"10.1002","volume":"13","author":[{"given":"Xia","family":"Shao","sequence":"first","affiliation":[{"name":"Center for Tumor Diagnosis and Therapy Jinshan Hospital Fudan University Shanghai 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