GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334206/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334206GEOGSEfalseSTK25 m6A modification regulates CD4+ T cell glycolysis mediated immune imbalance in systemic lupus erythematosusSystemic lupus erythematosus (SLE) is a complex autoimmune disease with an incompletely understood pathogenesis. N6-methyladenosine (m6A) has been implicated in immune regulation and disease progression, yet its role in disrupting immune homeostasis in SLE, particularly in CD4+ T-cell differentiation, remains poorly understood. In the present study, m6A-modified RNA immunoprecipitation sequencing (m6A-seq) and RNA sequencing (RNA-seq) of peripheral blood mononuclear cells from patients with SLE identified serine/threonine protein kinase 25 (STK25) as a candidate gene exhibiting abnormal m6A modification, and its expression was subsequently validated using reverse transcription-quantitative (RT-q)PCR. CD4+ T cells isolated from MRL/lupus-prone mice underwent lentiviral-mediated STK25 knockdown, and glycolytic activity was evaluated through measuring glucose uptake and lactate production. Western blotting and RT-qPCR demonstrated that STK25 knockdown reduced the expression of glycolysis-associated genes (glucose transporter 1, hexokinase 2, pyruvate kinase M2 and lactate dehydrogenase A) and the Treg-specific transcription factor Foxp3, while increasing the expression of the Th17- and Th2-associated transcription factors, RORĪ³t and Gata3. Flow cytometry further confirmed enhanced differentiation of Th17 and Th2 cells accompanied by a reduction in Treg cells, indicating disruption of immune homeostasis. Collectively, these findings suggested that aberrant m6A modification contributes to the downregulation of STK25 expression, thereby promoting glycolytic reprogramming and CD4+ T-cell subset imbalance in SLE. STK25 may therefore represent a potential therapeutic target for restoring immune homeostasis in SLE.2026/06/04GSE334206GSM9783360GSM9783364GSM9783353GSM9783363GSM9783352GSM9783351GSM9783362GSM9783361GSM9783350GSM9783346GSM9783357GSM9783356GSM9783355GSM9783354GSM9783365GSM9783349GSM9783348GSM9783359GSM9783358GSM978334724676334206Homo sapiens