STK25 m6A modification regulates CD4+ T cell glycolysis mediated immune imbalance in systemic lupus erythematosus

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, RORγt and Gata3.