Immunomodulatory effects of transforming growth factor-β in the liver

Members of the transforming growth factor-β (TGF-β) family are potent regulatory cytokinesthat affect multiple cell types of the immune system mediating pro-inflammatory or anti-inflammatoryresponses. In the liver, TGF-β is produced by a multitude of non-parenchymal liver cells including hepaticstellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), and dendritic cells (DCs)as well as natural killer (NK) T cells among other hepatic lymphocytes. The effect of TGF-β on other cells ishighly versatile. In concert with other soluble factors, it controls the maturation, differentiation and activity ofvarious T cell subsets that either prevent or actuate infections, graft-versus-host reactions, immune diseases,and cancer formation. During the last decades, it became evident that some TGFB1 polymorphisms areassociated with the pathogenesis of hepatic disease and that plasma TGF-β is a suitable biomarker to detectliver lesions. Moreover, since TGF-β has capacity to influence the quantity and quality of T cell subsets aswell as their activity, it is obvious that a well-balanced TGF-β activity is essential for liver homeostasis. Inthe present review, we highlight some pivotal functions of TGF-β in hepatic immunobiology. We discuss itsregulatory function on adaptive immunity, the impact on differentiation of various T cell subsets, its crosstalkwith Toll like receptor signaling, and its contribution to functional impairment of the liver.