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Atorvastatin (AT), a lipid\u2010lowering medicine, has shown promising immunomodulatory effects in certain inflammatory conditions. However, the immunoregulatory role of AT in ITP remains elusive. To investigate the effect of AT in the treatment of ITP, cluster of differentiation 4 (CD4)<jats:sup>+<\/jats:sup> T cells were isolated from patients with ITP and cultured with different dosages of AT. We found that AT significantly inhibited cell proliferation, led to cell cycle arrest, induced apoptosis, and repressed the activation of CD4<jats:sup>+<\/jats:sup> T cells <jats:italic>in vitro<\/jats:italic>. ITP murine models were then established, and results showed that AT treatment led to faster recovery of the platelet count to normal and exhibited comparable immunomodulatory function. Furthermore, we found the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT) and extracellular signal\u2010regulated kinase (ERK), as well as activation of rat sarcoma virus (RAS) were all reduced dramatically after AT treatment <jats:italic>in vitro<\/jats:italic>. In conclusion, our present study demonstrated that AT could reinstate the functions of CD4<jats:sup>+<\/jats:sup> T cells by inhibiting the excessive activation, proliferation, and survival of CD4<jats:sup>+<\/jats:sup> T cells in ITP via the RAS\/mitogen\u2010activated protein kinase kinase (MEK)\/ERK and the mTOR\/phosphatidylinositol\u20103 kinase (PI3K)\/AKT pathway. Therefore, we propose that AT could be used as a potential therapeutic option for ITP by restoring the over\u2010activated cellular immunity.<\/jats:p>","DOI":"10.1111\/bjh.17938","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T11:41:12Z","timestamp":1637926872000},"page":"530-541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Atorvastatin restores imbalance of cluster of differentiation 4 (CD4)<sup>+<\/sup> T cells in immune thrombocytopenia <i>in vivo<\/i> and <i>in vitro<\/i>"],"prefix":"10.1111","volume":"201","author":[{"given":"Pengcheng","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Hematology Qilu Hospital Cheeloo College of Medicine Shandong University Jinan 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