STAT1-GCLM axis promotes B-cell expansion in adenoid hypertrophy

Adenoid hypertrophy (AH) is a chronic inflammatory disorder characterized by pathological enlargement of nasopharyngeal lymphoid tissue, yet the mechanisms driving its progression remain unclear. Here, an LPS-induced inflammatory model was established in human immortalized B lymphoblastoid cells (B-LCLs). LPS stimulation increased IL-6 and TNF-α secretion and enhanced Ki67 expression, indicating an activated proliferative phenotype. RNA-seq analysis revealed marked transcriptional reprogramming, with significant enrichment of STAT signaling, glutathione metabolism, and ferroptosis-related pathways. Further experiments showed that inflammatory stimulation promoted STAT1 phosphorylation and nuclear translocation, whereas pharmacological inhibition of STAT signaling suppressed B-cell proliferation and partially reversed the inflammatory transcriptional program. Functionally, STAT inhibition partially reduced ATP production but further increased ROS accumulation, suggesting that STAT signaling contributes to both metabolic activation and redox maintenance. Mechanistically, GCLM was identified as a downstream target of STAT1 through differential gene overlap analysis and was validated by qPCR, western blotting, clinical sample analysis, and ChIP-qPCR. GCLM expression was elevated in the inflammatory model and in stage IV AH tissues, while STAT inhibition reduced GSH levels and enhanced ferroptosis-related changes. Consistently, GCLM knockdown decreased GSH content, increased lipid peroxidation, and altered ferroptosis-associated protein expression. Collectively, these findings demonstrate that the STAT1-GCLM axis sustains glutathione-dependent redox homeostasis and suppresses ferroptosis in B cells, thereby promoting AH progression.