Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases

Angelot, Fanny; Seillès, Estelle; Biichlé, Sabéha; Berda, Yaël; Gaugler, Béatrice; Plumas, Joël; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache‐Ottou, Francine

doi:10.3324/haematol.2009.010934

Cited by 83 publications

(83 citation statements)

References 49 publications

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“…In infectious conditions or in response to "danger" signals, pDC secrete IL-6 (7,8). In this paper, we reported increased IL-6 production by pDC in response to TGF-b, emphasizing the less recognized proinflammatory role of TGF-b (37).…”

Section: Discussionmentioning

confidence: 76%

“…Through IFN-a secretion, pDC can play a role in the antitumor effects induced by TLR7/9 ligand agonist (4-6) as well as in some autoimmune diseases (e.g., psoriasis and lupus) (3). However, pDC functions are not limited to IFN-a secretion because human and mouse pDC may secrete inflammatory cytokines such as IL-6 (7,8). Depending on the environmental signals, pDC have been described to initiate effective Th1 or Th2 cell responses (9).…”

mentioning

confidence: 99%

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TGF-β–Exposed Plasmacytoid Dendritic Cells Participate in Th17 Commitment

Bonnefoy

Couturier

Clauzon

et al. 2011

The Journal of Immunology

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TGF-β is required for both Foxp3+ regulatory T cell (Treg) and Th17 commitment. Plasmacytoid DCs (pDC) have been shown to participate to both Treg and Th17 commitment as well. However, few studies have evaluated the direct effect of TGF-β on pDC, and to our knowledge, no study has assessed the capacity of TGF-β–exposed pDC to polarize naive CD4+ T cells. In this paper, we show that TGF-β–treated pDC favor Th17 but not Treg commitment. This process involves a TGF-β/Smad signal, because TGF-β treatment induced Smad2 phosphorylation in pDC and blockade of TGF-β signaling with the SD208 TGF-βRI kinase inhibitor abrogated Th17 commitment induced by TGF-β–treated pDC. Moreover, TGF-β mRNA synthesis and active TGF-β release were induced in TGF-β–treated pDC and anti–TGF-β Ab blocked Th17 commitment. Unexpectedly, TGF-β treatment also induced increased IL-6 production by pDC, which serves as the other arm for Th17 commitment driven by TGF-β–exposed pDC, because elimination of IL-6–mediated signal with either IL-6– or IL-6Rα–specific Abs prevented Th17 commitment. The in vivo pathogenic role of TGF-β–treated pDC was further confirmed in the Th17-dependent collagen-induced arthritis model in which TGF-β–treated pDC injection significantly increased arthritis severity and pathogenic Th17 cell accumulation in the draining lymph nodes. Thus, our data reveal a previously unrecognized effect of TGF-β–rich environment on pDC ability to trigger Th17 commitment. Such findings have implications in the pathogenesis of autoimmune diseases or immune responses against mucosal extracellular pathogens.

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Section: Discussionmentioning

confidence: 76%

mentioning

confidence: 99%

TGF-β–Exposed Plasmacytoid Dendritic Cells Participate in Th17 Commitment

Bonnefoy

Couturier

Clauzon

et al. 2011

The Journal of Immunology

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“…In mouse PDC, TAK-1/MAP3K7 activates the mitogen-activated protein kinase (MAPK) pathway that upregulates costimulatory molecule expression (e.g., CD40, CD80 or CD86) 36 . Both human and mouse PDC have been shown to secrete TNF-α 4– 6, 45, 46 , IL-6 4– 6, 45, 46 , IL-8 45– 47 or granulocyte macrophage colony-stimulating factor (GM-CSF) 45 . This TLR-induced cytokine synthesis is regulated in PDC by the translocation of NF-κB, p38 MAPK and c-Jun N-terminal kinase (JNK) into the nucleus.…”

Section: The Innate Immune Functions Of Plasmacytoid Dendritic Cellsmentioning

confidence: 99%

“…These NET contain DNA fibers, histones, as well as a large amount of LL37 and HMGB1 52, 53 . Human PDC can also be activated by CD154 from activated platelets 54 or endothelial-derived microvesicles 6, 46 . Other PRR are present in the cytoplasm of PDC and dedicated to RNA virus recognition.…”

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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“…5 We then evaluated the role of LXR in PtdSerdependent MP internalization by PDC. After showing that MP uptake by PDC was PtdSer-dependent using AnxV, we observed that LXR stimulation significantly increased eFluor-labeled MP internalization by PDC ( Figure 1E).…”

mentioning

confidence: 99%