m⁶A-Mediated Glycolysis by IL-37 Drives T Cell Metabolic Reprogramming to Regulate Colitis

N6-methyladenosine (m⁶A) modification and T-cell metabolic reprogramming are increasingly recognized as critical drivers of inflammatory bowel disease (IBD). However, how the anti-inflammatory cytokine interleukin-37 intersects with m⁶A-mediated metabolic regulation remains unclear. Here, we show that IL-37 alleviates colitis by reducing global m⁶A levels and reshaping CD4⁺ T-cell metabolism. Mechanistically, IL-37 signals through its receptor SIGIRR to inhibit IRAK4 and JNK phosphorylation, suppress NF-κB p65 activation, and downregulate METTL14, thereby decreasing m⁶A deposition. The IL-37/METTL14 axis notably reduces m⁶A enrichment at the A2445 site in the 3'UTR of SLC2A1, destabilizing its mRNA and suppressing glycolysis. In vitro T-cell polarization and adoptive transfer of METTL14-overexpressing CD4⁺ T cells confirmed that this metabolic shift restrains Th1/Th17 differentiation while promoting Th2 expansion. Together, these findings reveal the IL-37/SIGIRR-METTL14-m⁶A axis as a novel regulator of T-cell metabolism and highlight SLC2A1 as a potential therapeutic target in IBD.