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In this study, we conducted a visual and quantitative analysis of cytoplasmic histones in CD4<jats:sup>+<\/jats:sup> T cells and discovered that effector CD4<jats:sup>+<\/jats:sup> T cells contain higher levels of cytoplasmic histones compared to na\u00efve T cells. We observed a significant increase in cytoplasmic histones following T cell receptor (TCR) activation, with further elevation during the differentiation of Th1 and Th17 cells. Interestingly, double\u2010stranded RNA (dsRNA) specifically enhanced cytoplasmic histones in Th17, but not in Th1 cells. Additionally, we confirmed that cytoplasmic H2B\u2010positive Th17 cells exhibited increased expression of inflammatory molecules, including pro\u2010inflammatory cytokines. Data are available via ProteomeXchange with identifier PXD063335. Importantly, CD4<jats:sup>+<\/jats:sup> T cells from peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) presented elevated levels of cytoplasmic histones. These findings define cytoplasmic histones as markers of proinflammatory CD4<jats:sup>+<\/jats:sup> T cells and suggest their potential as biomarkers for autoimmune disease.<\/jats:p>","DOI":"10.1111\/imm.13956","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T18:34:38Z","timestamp":1749062078000},"page":"105-115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytoplasmic Histone Is a Marker of Pro\u2010Inflammatory <scp>CD4<\/scp><sup>+<\/sup> T Cells"],"prefix":"10.1111","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4005-2832","authenticated-orcid":false,"given":"Bohan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong China"},{"name":"Guangdong Province Key Laboratory of Molecular Tumor Pathology  Guangzhou Guangdong 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