Engineered IL-10: A matter of affinity.

Pleiotropic roles of IL-10. Immune cells including regulatory T cells and B cells, ILCregs, macrophages, and DCs produce IL-10, which exerts both anti-inflammatory and pro-inflammatory effects. In an anti-inflammatory state, IL-10 suppresses inflammatory signals from several immune cells. In a pro-inflammatory state, IL-10 can induce CD8 T cells to release IFN-γ and granzyme B. The underlying mechanism that defines anti-inflammatory and pro-inflammatory activities of IL-10 depends on the binding affinity of IL-10 to its receptors (IL-10Rα and IL-10Rβ). The dimerization of the IL-10 complex activates STAT1/STAT3 and diversifies the biological effects of IL-10. In hindsight, high-affinity to IL-10Rβ leads to both anti-inflammatory and pro-inflammatory activities while low-affinity to IL-10Rβ only induces anti-inflammatory functions.