Dendritic cells (DCs) are key players in activation of the adaptive immune system by their ability of antigen presentation to and priming of T cells. An increasing body of evidence Suggests that DCS may also play an important role in induction of tolerance, predominantly by induction of regulatory T cells (T-reg). More recently, data have been published on how Toll-like receptor (TLR) ligands and cytokines affect DC differentiation, and how DC subsets might be involved in immunoregulation and tolerance rather than in T cell activation. The most important features of tolerance-inducing DCs appear to be their maturation state and their cytokine secretion pattern. The following types of tolerance-inducing DCs have been reported: immature DCs (DCsim) or DCs in the steady state (DCsst), DCsIL-10, semi-mature DCSTNF-alpha, semi-mature DCsIL-6. With this review article we Would like to discuss the aforementioned types of tolerogenic DCs with a focus on semi-mature DCsIL-6 and discuss their potential role in maintenance of (hepatic or intestinal) immune homeostasis and inflammatory diseases such as inflammatory bowel disease. (C) 2009 Elsevier GmbH. All rights reserved.