Tolerogenic dendritic cells and the priming of thymus-derived Tregs

Abstract

Dendritic cell (DCs) play a crucial role in both the innate and adaptive immune system. The immunogenic role of DCs, which involves activation by pattern recognition receptor (PRR), migration to the lymph nodes and activation of conventional T-cells (Tconvs), is well understood. However, DCs can also be tolerogenic and hinder immune activation. In the intestine, the presence of tolerogenic DCs can be beneficial to prevent chronic inflammation. However, in the context of tumors, where immune activation is wanted, there is also often immune suppression caused by tolerogenic DCs. In the past years, there has been a growing interest in not only understanding immunogenic but also tolerogenic DCs. This review aims to provide an overview of the various characteristics that have been described for tolerogenic DCs. In addition, we elaborate on the priming of regulatory T-cells (Tregs) by tolerogenic DCs. Tregs can be thymus derived (tTregs) or be peripherally induced from Tconv cells (pTregs). The traditional research focus has always been on pTregs. However, current studies reveal that it are the tTregs that are predominantly found in tissues like tumors and the intestine and that tTregs play an important role in mediating tolerance. The mechanism by which these tTregs end up in the tissues is not known. In this review, we established a model using existing information to explain how tTregs are primed by tolerogenic DCs and migrate to tissues like the intestine or tumors and play an important role in mediating tolerance