Figure 1.

Treg suppressive mechanisms. Tregs are able to suppress different cell types by direct and indirect mechanisms. Tregs can produce anti-inflammatory cytokines (IL-10, IL-35, and TGFβ) affecting T cells. In addition, they release perforin and granzyme, which damage target cell membrane leading to apoptosis. They can sequester, by the high expression of CD25, IL-2 from the microenvironment reducing effector T cells proliferation. IL-2 starvation reduces NKs from proliferating and exhibiting effector functions as well. Furthermore, NKs can be directly affected by Tregs in a membrane bound TGF-ß dependent manner. Tregs have been observed to have a direct effect on B-cells via PDL1/PD-1 interaction and DCs via both CTLA-4 and LAG-3. CTLA-4 blocks co-stimulation reducing CD80/CD86 expression and it induces upregulation of IDO. The expression of CD39 on Tregs mediate the conversion to ATP to adenosine and AMP and reduce T effector proliferation. Tregs can also skew monocyte toward M2 macrophages and prevent their differentiation in pro-inflammatory M1 macrophages. They can similarly induce a suppressive phenotype in neutrophils and reduce ILC2 cytokine secretion.