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Review
. 2010 Jul:236:11-27.
doi: 10.1111/j.1600-065X.2010.00916.x.

Programmed cell death of dendritic cells in immune regulation

Min Chen  1 , Jin Wang
Affiliations
Review

Programmed cell death of dendritic cells in immune regulation

Min Chen et al. Immunol Rev. 2010 Jul.

Abstract

Programmed cell death is essential for the maintenance of lymphocyte homeostasis and immune tolerance. Dendritic cells (DCs), the most efficient antigen-presenting cells, represent a small cell population in the immune system. However, DCs play major roles in the regulation of both innate and adaptive immune responses. Programmed cell death in DCs is essential for regulating DC homeostasis and consequently, the scope of immune responses. Interestingly, different DC subsets show varied turnover rates in vivo. The conventional DCs are relatively short-lived in most lymphoid organs, while plasmacytoid DCs are long-lived cells. Mitochondrion-dependent programmed cell death plays an important role in regulating spontaneous DC turnover. Antigen-specific T cells are also capable of killing DCs, thereby providing a mechanism for negative feedback regulation of immune responses. It has been shown that a surplus of DCs due to defects in programmed cell death leads to overactivation of lymphocytes and the onset of autoimmunity. Studying programmed cell death in DCs will shed light on the roles for DC turnover in the regulation of the duration and magnitude of immune responses in vivo and in the maintenance of immune tolerance.

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Figures

Figure 1
Figure 1. T cell-mediated killing of DCs
Activated T cells produce FasL and also secrete cytolytic granules containing perforin and granzyme B. DCs can be killed by antigen-specific T cells through Fas- and perforin-dependent manners. Triggering of Fas can lead to the activation of caspase-8 and caspase-10 (in humans) and trigger a downstream caspase cascade to induce apoptosis. Cytolytic components secreted by T cells depend on perforin to enter DCs. Granzyme B may direct cleave effector caspases to induce apoptosis. Other components may also induce other forms of programmed cell death. However, alternative cell death pathways in DCs have not been well characterized.
Figure 2
Figure 2. Interactions of DCs with T effector cells and Treg cells in immune responses
DCs process and present antigens to activation antigen-specific T effector cells, while T effector cells may provide survival signals to DCs. Treg cells inhibit DCs potentially through suppression of DC renewal. After activation, however, T effector cells may kill antigen-presenting DCs through Fas- and perforin-dependent manner. Treg cells may induce cell death in DCs, however, a molecular mechanism for Treg-mediated suppression of DC is unknown. Most activation T cells undergo programmed cell death (PCD) after the clearance of antigens, while some will survive as memory cells. Whether DC influence PCD in activated T cells and the generation will be interesting to investigate.
Figure 3
Figure 3. Regulation of mitochondrion-dependent cell death in DCs
Conventional DCs have limited expression of Bcl-2 that is correlated with high rate of spontaneous cell death. Signaling from TLRs can induce the expression of Bcl-xL to promote DC survival.
See this image and copyright information in PMC

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