Figure 5. MSCs release IL-10 to suppress TGF-β release and decrease α-SMA expression. During a prolonged inflammatory response, recruited Th2-lymphocytes release of IL-13 and IL-4 to induce the polarization of macrophage type 1 (M1) into macrophage type 2 (M2). Activated M2 and Th2 cells release TGF-β, to activate quiescent HSCs, which differentiate into MFs (active HSCs), which are characterized by α-SMA expression, resulting in the massive production of ECM. MSCs supress the release of TGF-β from Kupffer and M2 cells by releasing IL-10. The binding of IL-10 to receptors on target cells may activate the promoters of the suppressor of cytokine signaling 3 (SOCS3), leading to the decreased expression of TGF-β. IL-10-releasing MSCs inhibit the activation of HSCs by competing against TGF-β for receptor binding, inducing apoptosis in the activated HSCs. Furthermore, IL-10 also downregulates the expression of profibrotic genes and up-regulates anti-fibrotic hepatic genes.
