Low‐dose decitabine promotes M2 macrophage polarization in patients with primary immune thrombocytopenia via enhancing KLF4 binding to PPARγ promoter

• DOI: 10.1002/ctm2.1344
• Publication Date: 2023-07-25T03:50:23Z
• Authors: Xia Shao; Pengcheng Xu; Lili Ji; Boting Wu; Yanxia Zhan; Xibing Zhuang; Yang Ou; Fanli Hua; Lihua Sun; Feng Li; Xiangdong Wang; Hao Chen; Yunfeng Cheng
• Keywords: Decitabine; KLF4; Primary (astronomy)

Background The first‐line therapy is effective for the treatment of primary immune thrombocytopenia (ITP); however, maintaining long‐term responses remains challenging. Low‐dose decitabine (DAC) has been adopted to treat refractory ITP, while its role in macrophage polarization not fully understood. We aimed investigate mechanistic DAC M2 and evaluated therapeutic effect ITP. Methods monocytes were identified by flow cytometry from peripheral blood mononuclear cells healthy controls (HCs) ITP patients. expression PPARγ, Arg‐1, DNMT3b NLRP3, together with IL‐10 plasma levels was measured examine function. Bisulfite‐sequencing PCR used evaluate methylation status PPARγ promoter, binding affinity KLF4 Cut&Tag. A sh‐PPARγ THP‐1 cell line created verify if low‐dose DAC‐modulated PPARγ‐dependent. passive models effects modulating immunomodulatory function macrophages. NLRP3 inflammasome reactive oxygen species also tested understand downstream PPARγ. Results impaired immunoregulation observed After high‐dose dexamethasone (HD‐DXM) treatment, increased significantly elevated Arg‐1 CR promoted a PPARγ‐dependent way via demethylating promoter especially sites. alleviated mice restoring M1/M2 balance fine‐tuning modulation might physiologically antagonize inflammasome. Conclusions due demethylation within thus enhanced