Id2 orchestrates IL-33-driven metabolic reprogramming in pathogenic Th2 cells (ChIP-seq)

Id2 transcriptionally represses Pten by sequestering E proteins at its promoter, amplifying PI3K‑AKT signaling and glycolytic flux, which supports histone acetylation at Il1rl1 and Il5. Id2‑deficient Th2 cells fail to establish this epigenetic state; pyruvate supplementation rescues the defect.

Pharmacological Id2 inhibition attenuates Tpath2 responses and airway inflammation in vivo, and cross‑species analysis confirms conserved PTEN dynamics in human asthma. Thus, the IL‑33–Id2–PI3K‑AKT axis represents a metabolic–epigenetic checkpoint and therapeutic target for allergic airway disease.