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In this study, we investigated the role of histone deacetylase 1 (HDAC1) in sepsis-induced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell exhaustion, a key driver of immunosuppression. Clinical analyses of patients with sepsis revealed that reduced peripheral blood lymphocyte levels, particularly CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell depletion, strongly correlated with worsened outcomes. In a murine sepsis model, single-cell RNA-Seq revealed a significant decrease in the proportion of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and an increase in the proportion of exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in mouse lungs. Adoptive transfer of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells effectively reduced sepsis mortality by preserving organ function. We further demonstrated that HDAC1 expression was significantly upregulated in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from patients with sepsis. In vitro studies showed that HDAC1 inhibition preserved CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell function by maintaining T cell activity and reducing the expression of inhibitory molecules such as PD-1. Pharmacological inhibition of HDAC1 reduced mortality and reversed CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell exhaustion by restoring the balance between activator protein-1 (AP-1) and nuclear factor of activated T cells (NFAT). Additionally, we found that HDAC1 directly interacted with NFAT1, promoting its nuclear translocation and further enhancing the expression of inhibitory molecules. Our findings highlight HDAC1 as a potential therapeutic target for sepsis-induced immunosuppression. By elucidating the molecular mechanisms underlying HDAC1-mediated immunosuppression, we have provided potential strategies for developing immunomodulatory therapies for the treatment of sepsis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.197224","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T16:21:34Z","timestamp":1771863694000},"source":"Crossref","is-referenced-by-count":2,"title":["HDAC1 modulates sepsis-induced immunosuppression by driving the exhaustion of CD8+ T cells"],"prefix":"10.1172","volume":"11","author":[{"given":"Liu","family":"Di","sequence":"first","affiliation":[{"name":"Department of Trauma Medical Center, and"},{"name":"Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China."},{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, 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