Plasmacytoid Dendritic Cells Play a Major Role in Apoptotic Leukocyte-Induced Immune Modulation

Bonnefoy, Francis; Perruche, Sylvain; Couturier, Mélanie; Sedrati, A.; Sun, Yu; Tiberghien, Pierre; Gaugler, Béatrice; Saas, Philippe

doi:10.4049/jimmunol.1001523

Cited by 59 publications

(77 citation statements)

References 44 publications

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“…To avoid alloreactivity against pDC, we then used a full H-2-mismatched acute GvHD model with an irradiation conditioning regimen (23), in which lethally conditioned host BALB/c mice were reconstituted with C57BL/6 BM cells and received C57BL/6 donor T cells 14 d later to trigger acute GvHD. Recipient pDC were described depleted by the conditioning regimen in that context (32), but BMT allowed donor hematopoiesis and, contextually, reconstitution of the pDC pool from the donor origin (32). GvHD occurred 1 wk after T cell transfer (Fig.…”

Section: T Cell-dependent Inflammation Affects Pdc Survivalmentioning

confidence: 99%

Plasmacytoid Dendritic Cells Die by the CD8 T Cell–Dependent Perforin Pathway during Acute Nonviral Inflammation

Mossu

Daoui

Bonnefoy

et al. 2016

The Journal of Immunology

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Regulation of the inflammatory response involves the control of dendritic cell survival. To our knowledge, nothing is known about the survival of plasmacytoid dendritic cells (pDC) in such situation. pDC are specialized in type I IFN (IFN-I) secretion to control viral infections, and IFN-I also negatively regulate pDC survival during the course of viral infections. In this study, we asked about pDC behavior in the setting of virus-free inflammation. We report that pDC survival was profoundly reduced during different nonviral inflammatory situations in the mouse, through a mechanism independent of IFN-I and TLR signaling. Indeed, we demonstrated that during inflammation, CD8+ T cells induced pDC apoptosis through the perforin pathway. The data suggest, therefore, that pDC have to be turned down during ongoing acute inflammation to not initiate autoimmunity. Manipulating CD8+ T cell response may therefore represent a new therapeutic opportunity for the treatment of pDC-associated autoimmune diseases, such as lupus or psoriasis.

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Section: T Cell-dependent Inflammation Affects Pdc Survivalmentioning

confidence: 99%

Plasmacytoid Dendritic Cells Die by the CD8 T Cell–Dependent Perforin Pathway during Acute Nonviral Inflammation

Mossu

Daoui

Bonnefoy

et al. 2016

The Journal of Immunology

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“…This has been demonstrated by in vivo PDC depletion studies 24, 56 . For instance, PDC exert immunoregulatory functions in the lung, preventing deleterious asthmatic reactions 24 .…”

Section: The Innate Immune Functions Of Plasmacytoid Dendritic Cellsmentioning

confidence: 64%

“…Receptors expressed by PDC, such as immunoglobulin-like transcript 7 61 or CD303 62 may also inhibit TLR7/9-mediated type I IFN production. In addition, PDC can produce, under certain circumstances, high levels of immunosuppressive cytokines, such as IL-10 19, 25 or TGF-β 56, 63 . In addition, PDC participate in the maintenance of immune tolerance via the induction and/or expansion of regulatory T cells (please refer to Refs# 7, 63 ; this is out of the scope of this review).…”

Section: The Innate Immune Functions Of Plasmacytoid Dendritic Cellsmentioning

confidence: 99%

Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

Saas¹,

Varin²,

Perruche³

et al. 2017

F1000Res

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There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β). Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases. Recent data support the idea that the glycolytic pathway (or glycolysis), as well as lipid metabolism (including both cholesterol and fatty acid metabolism) may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR) 7/9 triggering. Some differences may be related to the origin of PDC (human versus mouse PDC or blood-sorted versus FLT3 ligand stimulated-bone marrow-sorted PDC). The kinetics of glycolysis may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR, explaining a delayed glycolysis. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR]) in PDC or through limiting intracellular cholesterol pool size (by statins or LXR agonists) in these cells. Finally, lipid-activated nuclear receptors ( i.e., LXR or peroxisome proliferator activated receptor) may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations where PDC play a detrimental role.

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“…However, despite limited capacity to uptake apoptotic cells, PDCs may play a role in apoptotic cell-induced immunomodulation by interacting with other immune cells: macrophages and pTregs [85].…”

Section: Future Science Groupmentioning

confidence: 99%

“…Delayed apoptotic cell elimination [83]; Subcellular fragment uptake as attested by endocytosis of apoptotic cell-derived membrane microparticles or apoptotic bodies [83,84], but not whole apoptotic cells [85,86];…”

Section: Future Science Groupmentioning

confidence: 99%

Prospects of Apoptotic Cell-Based Therapies for Transplantation and Inflammatory Diseases

2013

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Apoptotic cell removal or interactions of early-stage apoptotic cells with immune cells are associated with an immunomodulatory microenvironment that can be harnessed to exert therapeutic effects. While the involved immune mechanisms are still being deciphered, apoptotic cell infusion has been tested in different experimental models where inflammation is deregulated. This includes chronic and acute inflammatory disorders such as arthritis, contact hypersensitivity and acute myocardial infarction. Apoptotic cell infusion has also been used in transplantation settings to prevent or treat acute and chronic rejection, as well as to limit acute graft-versus-host disease associated with allogeneic hematopoietic cell transplantation. Here, we review the mechanisms involved in apoptotic cell-induced immunomodulation and data obtained in preclinical models of transplantation and inflammatory diseases.

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Plasmacytoid Dendritic Cells Play a Major Role in Apoptotic Leukocyte-Induced Immune Modulation

Cited by 59 publications

References 44 publications

Plasmacytoid Dendritic Cells Die by the CD8 T Cell–Dependent Perforin Pathway during Acute Nonviral Inflammation

Plasmacytoid Dendritic Cells Die by the CD8 T Cell–Dependent Perforin Pathway during Acute Nonviral Inflammation

Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

Prospects of Apoptotic Cell-Based Therapies for Transplantation and Inflammatory Diseases

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