Control of TNF-Induced Dendritic Cell Maturation by Hybrid-Type <i>N</i>-Glycans

Schlickeiser, Stephan; Stanojlović, Svetlana; Appelt, Christine; Vogt, Katrin; Vogel, Siegfried; Haase, Stefanie; Ritter, Thomas; Volk, Hans‐Dieter; Pleyer, Uwe; Sawitzki, Birgit

doi:10.4049/jimmunol.1003410

Cited by 7 publications

(7 citation statements)

References 57 publications

(61 reference statements)

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“…However, recent studies showed that Dectin-2 also recognizes lipomannan, mannoprotein and mannosylated O-antigen that contain terminal mannose [9, 11, 23]. Interestingly, in vertebrates, high mannose-type N-linked glycans are also found on particular type of DC [24]. Gusb is known to contain high mannose type glycans [18].…”

Section: Discussionmentioning

confidence: 99%

C-Type Lectin Receptor Dectin-2 Binds to an Endogenous Protein β-Glucuronidase on Dendritic Cells

Mori¹,

Shibata²,

Yamasaki³

2017

PLoS ONE

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C-type lectin receptors (CLRs) recognize pathogen-derived ligands and abnormal self that trigger protective immune responses. However, the precise nature of self ligands recognized by CLRs remains to be determined. Here, we found that Dectin-2 recognizes bone marrow-derived dendritic cells (BMDCs) using Dectin-2-expressing reporter cells. This activity was inhibited by an excessive amount of mannose, and by the mutation of mannose-binding motif in Dectin-2. β-glucuronidase (Gusb) was identified as a protein bound to Dectin-2 and mutations of N-glycosylation sites in Gusb impaired the binding of Gusb to Dectin-2. Overexpression of Gusb in a macrophage cell line conferred an ability to stimulate Dectin-2-expressing reporter cells. Our study suggests that a glycosylated protein with mannose-related structure is recognized by Dectin-2.

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Section: Discussionmentioning

confidence: 99%

C-Type Lectin Receptor Dectin-2 Binds to an Endogenous Protein β-Glucuronidase on Dendritic Cells

Mori¹,

Shibata²,

Yamasaki³

2017

PLoS ONE

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“…A vast amount of data indicate that TNF-α induces the maturation of immature DCs and, moreover, that it induces transcellular migration of DCs, which depends on the production of IL-8. 53,54 The migratory DCs activate T-cells and subsequently initiate the adaptive immune response against invading bacteria and viruses. 55 However, recruitment of TRIF associated with TLR4 results in the activation and nuclear translocation of IRF3, an essential transcription factor generally involved in induction of type I IFN and pro-inflammatory cytokines, such as IL-12, IL-18 and IL-23, in wild type DCs.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the innate immune responses of porcine monocyte-derived dendritic cells and splenic dendritic cells stimulated with LPS

Çınar

Fan

et al. 2014

Innate Immun

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Dendritic cell (DC) subsets form a remarkable cellular network that regulate innate and adaptive immune responses. Although pigs are the most approximate model to humans, little is known about the regulation of monocyte-derived DCs (moDCs) and splenic DCs (SDCs) in the initiation of immune responses under inflammatory conditions. We investigated the activation and maturation of porcine moDC and SDC subpopulations following LPS stimulation. Porcine monocytes that would differentiate into moDCs were isolated. SDCs were isolated directly from the porcine spleen. Following LPS stimulation, phagocytosis activity, TLR4/MyD88-dependent gene expression, co-stimulatory molecule, and pro-inflammatory cytokine (TNF-α, IL-1β) and chemokine (IL-8) expressions were increased in both cell subsets. Furthermore, moDCs showed higher levels of gene and protein expression compared with SDCs. Interestingly, moDCs were found to be more responsive via the TLR4/TRAF-dependent signalling pathway of activation. Only SDCs expressed higher level of IL-12p40 gene and protein, whereas, IFN-γ gene and protein expression were likely to be unchanged after LPS stimulation in both cell subtypes. These data demonstrate that porcine moDCs display a greater ability to initiate innate immune responses, and could be used as a model to investigate immune responses against Ags.

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“…FACS data were analyzed using FlowJo software (TreeStar Inc., OR, USA). For proinflammatory cytokine-induced maturation of DCs, BMDCs were treated with CCNVs and recombinant TNF-α (100 ng/ml) and IFN-γ (20 ng/ml) (BioLegend) 34 , 35 . Then, the BMDCs were detached and stained with the following antibodies: APC-Cy7 anti-mouse CD11c antibody, PE anti-mouse CD80 antibody and APC anti-mouse CD86 antibody (BioLegend).…”

Section: Methodsmentioning

confidence: 99%

Senescent cancer cell-derived nanovesicle as a personalized therapeutic cancer vaccine

et al. 2023

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The development of therapeutic cancer vaccines (TCVs) that provide clinical benefits is challenging mainly due to difficulties in identifying immunogenic tumor antigens and effectively inducing antitumor immunity. Furthermore, there is an urgent need for personalized TCVs because only a limited number of tumor antigens are shared among cancer patients. Several autologous nanovaccines that do not require the identification of immunogenic tumor antigens have been proposed as personalized TCVs. However, these nanovaccines generally require exogenous adjuvants (e.g., Toll-like receptor agonists) to improve vaccine immunogenicity, which raises safety concerns. Here, we present senescent cancer cell-derived nanovesicle (SCCNV) as a personalized TCV that provides patient-specific tumor antigens and improved vaccine immunogenicity without the use of exogenous adjuvants. SCCNVs are prepared by inducing senescence in cancer cells ex vivo and subsequently extruding the senescent cancer cells through nanoporous membranes. In the clinical setting, SCCNVs can be prepared from autologous cancer cells from the blood of liquid tumor patients or from tumors surgically removed from solid cancer patients. SCCNVs also contain interferon-γ and tumor necrosis factor-α, which are expressed during senescence. These endogenous cytokines act as adjuvants and enhance vaccine immunogenicity, avoiding the need for exogenous adjuvants. Intradermally injected SCCNVs effectively activate dendritic cells and tumor-specific T cells and inhibit primary and metastatic tumor growth and tumor recurrence. SCCNV therapy showed an efficacy similar to that of immune checkpoint blockade (ICB) therapy and synergized with ICB. SCCNVs, which can be prepared using a simple and facile procedure, show potential as personalized TCVs.

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Control of TNF-Induced Dendritic Cell Maturation by Hybrid-Type N-Glycans

Cited by 7 publications

References 57 publications

C-Type Lectin Receptor Dectin-2 Binds to an Endogenous Protein β-Glucuronidase on Dendritic Cells

C-Type Lectin Receptor Dectin-2 Binds to an Endogenous Protein β-Glucuronidase on Dendritic Cells

Comparison of the innate immune responses of porcine monocyte-derived dendritic cells and splenic dendritic cells stimulated with LPS

Senescent cancer cell-derived nanovesicle as a personalized therapeutic cancer vaccine

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