Abstract
Peripheral immune tolerance requires a controlled balance between the maintenance of self-tolerance and the capacity to engage protective immune responses against pathogens. Dendritic cells (DCs) serve as sentinels of the immune system by sensing environmental and inflammatory signals, and play an essential role in the maintenance of immune tolerance. To achieve this, DC play a key role in dictating the outcome of immune responses by influencing the balance between inflammatory or Foxp3+ regulatory T (Treg) cell responses. At the heart of this immunological balance is a finely regulated DC and Treg cell crosstalk whereby Treg cells modulate DC phenotype and function, and DC drive the differentiation of Foxp3+ Treg cells in order to control immune responses. This review will focus on recent advances, which highlight the importance of this bidirectional DC and Treg cell crosstalk during the induction of tolerance and organ-specific autoimmunity. More specifically, we will discuss how Treg cells modulate DC function for the suppression of inflammatory responses and how DC subsets employ diverse mechanisms to drive differentiation of Treg cells. Finally, we will discuss the therapeutic potential of tolerogenic DCs for the induction of tolerance in autoimmune diseases.
Highlights
Immune tolerance consists of two main processes, namely central and peripheral tolerance
We showed that non-obese diabetic (NOD).Idd3BL6 Dendritic cells (DCs) are more potent activators of the balance between inflammatory or Foxp3+ regulatoryT (Treg) cells functions in vitro and in vivo, and this increased capacity of congenic DCs to prime Treg cells is attributed to their ability to produce IL-2
Tolerogenic DCs has a dual role, for example in cancer, a profound defect in DCs function are associated with accumulation of immature DCs in tumors where DCs are unable to initiate antitumor immune responses while contributes to the recruitment, expansion and function of Treg cells
Summary
Immune tolerance consists of two main processes, namely central and peripheral tolerance. Treg cells constitute 1–10% of thymic and peripheral CD4+ T cells in humans and mice, and arise during a thymic selection (Sakaguchi, 2000) They are characterized by the constitutive expression of the IL-2Rα chain (CD25) and expression of the forkhead winged helix transcriptional regulator Foxp (Hori et al, 2003). DCs exist as a distinct subset and differ in their ontogeny, surface molecule expression, and biological functions (Banchereau and Steinman, 1998; Steinman and Nussenzweig, 2002). These factors seems to determine the T cells polarizing signals and type T cells responses induced by DCs namely Th1, Th2, Th17, or Treg cells. All DCs are able to prime T cells, they differ in their in vivo niches, migration, function, and requirements www.frontiersin.org
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