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Since N<jats:sup>6<\/jats:sup>\u2010methyladenosine (m6A) RNA methylation impacts on immunocyte function and antitumor immunity, it is predictable that m6A RNA methylation may result in immune microenvironment disorder. Here, we attempted to verify this hypothesis. We used single\u2010sample gene set enrichment analysis (ssGSEA)\u00a0to investigate the infiltration abundance of immunocytes, single\u2010cell RNA\u2010Seq to identify key m6A regulator, and a doxorubicin (Dox)\u2010induced DCM mouse model to confirm our findings. ssGSEA revealed a higher infiltration abundance of CD8<jats:sup>+<\/jats:sup> T lymphocytes, NK cells, monocytes, and B<jats:sup>+<\/jats:sup> lymphocytes in DCM myocardium tissue. Single\u2010cell RNA\u2010Seq indicated a critical role of IGFBP2 in DCM. Cross\u2010checking analysis hinted an interaction between IGFBP2 and NSUN5, ALYREF, RRP8, and ALKBH3. Mechanically, IGFBP2\u2010mediated RNA methylation deteriorated the immune microenvironment and thus increased the risk of DCM by enhancing CD8<jats:sup>+<\/jats:sup> T lymphocyte, NK cell, monocyte, B<jats:sup>+<\/jats:sup> lymphocyte infiltration and activating check\u2010point, MHC\u2010I, and T cell co\u2010stimulation signaling pathways. In the DCM mouse model, echocardiography indicated a significant reduction in ejection fraction (EF)\u00a0and fractional shortening (FS)\u00a0and an increase in left ventricular internal dimensions at systole (LVIDs)\u00a0and diastole (LVIDd).\u00a0MASSON staining indicated an increased fibrosis in myocardium tissue. qPCR and immunofluorescence staining indicated a significant increase in mRNA and protein levels of IGFBP2. The present study indicated that IGFBP2\u2010mediated RNA methylation remodeled the immune microenvironment and increased the risk of DCM. IGFBP2 may serve as potential therapeutic target for DCM.<\/jats:p>","DOI":"10.1002\/jcp.31085","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T07:04:45Z","timestamp":1689923085000},"page":"2282-2292","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["m6A regulator\u2010mediated RNA methylation modification remodels immune microenvironment in dilated cardiomyopathy"],"prefix":"10.1002","volume":"238","author":[{"given":"Zhi","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Geriatrics Zhongnan Hospital of Wuhan University, Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Zhongnan Hospital of Wuhan University, Wuhan University Wuhan 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