The Importance of Dendritic Cells in Maintaining Immune Tolerance

Abstract

Immune tolerance is necessary to prevent the immune system from reacting against self, and thus to avoid the development of autoimmune diseases. In this review, we discuss key findings that position dendritic cells (DCs) as critical modulators of both thymic and peripheral immune tolerance. Although DCs are important for inducing both immunity and tolerance, increased autoimmunity associated with decreased DCs suggests their nonredundant role in tolerance induction. DC-mediated T cell immune tolerance is an active process that is influenced by genetic variants, environmental signals, as well as the nature of the specific DC subset presenting Ag to T cells. Answering the many open questions with regard to the role of DCs in immune tolerance could lead to the development of novel therapies for the prevention of autoimmune diseases.

Figure 1

DC-mediated central tolerance. Migratory CD11b⁺CCR2⁺DCs and CCR9⁺ pDCs migrate from periphery to the thymic cortex and induce tolerance to peripheral self-antigens by inducing apoptosis of autoreactive thymocytes. Migratory DCs also promote Treg differentiation. CD8a⁺ resident DCs induce apoptosis of thymocytes reactive to self-antigens and promote Treg differentiation and survival.

Figure 2

DC-mediated peripheral tolerance. cDCs and pDCs induce tolerance by promoting Treg differentiation or function. cDCs can also induce periperhal tolerance by inducing T cell anergy (not shown) or T cell deletion. In inflammatory conditions, cDCs and pDCs promote T cell activation.