Figure 4.

Sirt1 played a role in T-cell activation, differentiation and tolerance. In T cells, Sirt1 serves as a negative regulator of T-cell activation by deacetylating activator protein 1 (AP-1), but over-expression of Sirt1 drives T-cell tolerance. Sirt1 could also limit T-cell proliferation in response to interleukin-2 (IL-2) by both down-regulating signal transducer and activator of transcription 5 (STAT5) expression and suppressing pSTAT5 signalling. During HIV infection, Sirt1 inhibition leads to immune hyperactivation induced by Tat and T-cell apoptosis respectively by targeting p65 and p53. Sirt1 could also regulate T-cell activation and IL-2 transcription by controlling Bclaf1 and nuclear factor of activated T-cell transcription factor (NFAT). Besides, modulating Sirt1 activity in T cells regulates Foxp3 protein levels as well as the number and suppressive capacity of induced regulatory T cells. Although the Sirt1–STAT3 axis has not been proved in T cells directly, it is likely that Sirt1 regulates T-cell differentiation through deacetylating STAT3.