Blockade of HMGB1 or macrophage PTEN deletion activates PI3K/PDK1/Akt and β-catenin signaling, which in turn enhances macrophage TGF-β leading to increased Foxp3 Treg induction while inhibiting Th17 cell differentiation during sepsis-induced lung injury. Here, HMGB1 is linked to Sepsis.