Figure 2.

Targets of SIRT1 in the immune responses. SIRT1 inhibits immune activity via deacetylation of multiple targets. Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1) are key transcription factors involved in the production of inflammatory cytokines and immune hyperactivation. B-cell lymphoma 2-associated factor 1 (Bclaf1) was found to be regulated by NF-κB, which is associated with immune cell survival. SIRT1 restrains the high-mobility group box 1 (HMGB1) exocytosis to exert protective and anti-inflammatory effects by inhibiting the HMGB1/TLR4/MyD88/NF-κB signaling pathway. Fork head box P3 (FOXP3), signal transducer and activator of transcription 3 (STAT3), and retinoid acid receptor-related orphan receptor gamma t (RORγt) are pivotal regulators of T cell differentiation into regulatory T cells (Tregs) and Th17 cells. Th9 cell differentiation and the release of IL-9 are regulated through SIRT1-mTOR-HIF1α signaling.