Immune Regulation through Mitochondrion-Dependent Dendritic Cell Death Induced by T Regulatory Cells

Chen, Min; Felix, Kumar; Wang, Jin

doi:10.4049/jimmunol.1101834

Cited by 15 publications

(15 citation statements)

References 78 publications

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“…Paradoxically, it was also suggested that impaired apoptosis of DCs might increase DC numbers and cause autoimmunity 37–39 . However, it remains unclear whether the in vivo blockade of apoptosis was limited to DCs in these studies; indeed, some of these studies used a Cre-deleter strain that has a broad deletion range (BOX 1).…”

Section: The Role Of Dcs In Autoimmunity: General Aspectsmentioning

confidence: 99%

The role of dendritic cells in autoimmunity

et al. 2013

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Dendritic cells (DCs) initiate and shape both the innate and adaptive immune responses. Accordingly, recent evidence from clinical studies and experimental models implicates DCs in the pathogenesis of most autoimmune diseases. However, fundamental questions remain unanswered concerning the actual roles of DCs in autoimmunity, both in general and, in particular, in specific diseases. In this Review, we discuss the proposed roles of DCs in immunological tolerance, the effect of the gain or loss of DCs on autoimmunity and DC-intrinsic molecular regulators that help to prevent the development of autoimmunity. We also review the emerging roles of DCs in several autoimmune diseases, including autoimmune myocarditis, multiple sclerosis, psoriasis, type 1 diabetes and systemic lupus erythematosus.

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Section: The Role Of Dcs In Autoimmunity: General Aspectsmentioning

confidence: 99%

The role of dendritic cells in autoimmunity

et al. 2013

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“…On the other hand, articles published in 2011 demonstrate that T regulatory cells are controlled by the apoptosis of dendritic cells [208] and by caspase processed cytokines [189]. Furthermore, T regulatory cells control the onset and perpetuation of autoimmunity acting on Th2 cells [207], through the expression of CD103 [197], and on CD8+ cytotoxic cells [196].…”

Section: T Cell Subpopulationsmentioning

confidence: 96%

Autoimmunity in 2011

Selmi

2012

Clinic Rev Allerg Immunol

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The mechanisms leading to the onset and perpetuation of systemic and tissue-specific autoimmune diseases are complex, and numerous hypotheses have been proposed or confirmed over the past 12 months. It is particularly of note that the number of articles published during 2011 in the major immunology and autoimmunity journals increased by 3 % compared to the previous year. The present article is dedicated to a brief review of the reported data and, albeit not comprehensive of all articles, is aimed at identifying common and future themes. First, clinical researchers were particularly dedicated to defining refractory forms of diseases and to discuss the use and switch of therapeutic monoclonal antibodies in everyday practice. Second, following the plethora of genome-wide association studies reported in most multifactorial diseases, it became clear that genomics cannot fully explain the individual susceptibility and additional environmental or epigenetic factors are necessary. Both these components were widely investigated, both in organ-specific (i.e., type 1 diabetes) and systemic (i.e., systemic lupus erythematosus) diseases. Third, a large number of 2011 works published in the autoimmunity area are dedicated to dissect pathogenetic mechanisms of tolerance breakdown in general or in specific conditions. While our understanding of T regulatory and Th17 cells has significantly increased in 2011, it is of note that most of the proposed lines of evidence identify potential targets for future treatments and should not be overlooked.

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“…Treg cells in tumor tissues have also been reported to kill DCs in a perforin-dependent manner (74). We have found that activated Treg cells could directly induce cell death in DCs in a Bax and Bak–dependent manner to inhibit DC-dependent immune responses (84). Therefore, Treg-mediated killing of DCs could provide an alternative mechanism for immunosuppression by Treg cells (Fig.…”

Section: Treg Cells On DC Survivalmentioning

confidence: 99%

“…We observed a small but reproducible increase of CD4 + FoxP3 + Treg cells in autoimmune mice harboring apoptosis deficiency in DCs (1). We have also identified that deficiencies in Bax and Bak enable DC to be resistant to killing by Treg cells to over-activate T effector cells (84). However, other mechanisms by which apoptosis-deficient DCs overcome the inhibition by Treg cells to over-activate T effector cells remain to be elucidated.…”

Section: Treg Cells On DC Survivalmentioning

confidence: 99%

“…It has been reported that Bax −/− Bak −/− mice are defective in thymic negative selection for autoreactive T cells (88). We found that DC-specific knockout of Bax and Bak, induced spontaneous T cell activation and autoimmunity in mice (84). Bax −/− Bak −/− DCs showed a defect in spontaneous cell death and were resistant to killing by FoxP3 + T regulatory cells compared to wild type DCs (84).…”

Section: Treg Cells On DC Survivalmentioning

confidence: 99%

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Regulation of Immune Responses by Spontaneous and T cell-mediated Dendritic Cell Death

Chen

Wang²

2012

J Clin Cell Immunol

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In response to antigen stimulations, cells in the immune system undergo dynamic activation, differentiation, expansion and turnover. Programmed cell death is important for maintaining homeostasis of different cell types in the immune system. Dendritic cells (DCs) are a heterogeneous population of antigen presenting cells that capture, process and present antigens to stimulate lymphocytes. DCs have also emerged as major regulators of both innate and adaptive immune responses. Conventional myeloid DCs are relatively short-lived compared to lymphocytes in lymphoid organs. Mitochondrion-dependent apoptosis governed by Bcl-2 family members plays a major role in regulating spontaneous DC turnover. Killing of DCs by antigen-specific T cells also provides a negative feedback mechanism to restrict the duration and the scope of immune responses. Defects in cell death in DCs lead to DC accumulation, resulting in overactivation of lymphocytes and the development of autoimmunity in mice. Programmed cell death in DCs may play essential roles in the regulation of the duration and magnitude of immune responses, and in the protection against autoimmunity and uncontrolled inflammation.

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Immune Regulation through Mitochondrion-Dependent Dendritic Cell Death Induced by T Regulatory Cells

Cited by 15 publications

References 78 publications

The role of dendritic cells in autoimmunity

The role of dendritic cells in autoimmunity

Autoimmunity in 2011

Regulation of Immune Responses by Spontaneous and T cell-mediated Dendritic Cell Death

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