Immunomodulatory Bonds of the Partnership between Dendritic Cells and T Cells

Bourque, Jessica; Hawiger, Daniel

doi:10.1615/critrevimmunol.2018026790

Cited by 69 publications

(65 citation statements)

References 241 publications

(253 reference statements)

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“…Figure 4 illustrates gene expression changes for a panel of molecules reported to affect DC‐mediated T‐cell activation [35‐38], including maturation markers analyzed above with flow cytometry. For cDC1 and their expression of CD40, CD80, CD83, TNFRSF18 (GITR), and CD274 (PD‐L1), the highest upregulation was detected with Poly(I:C), followed by Gardiquimod and Pam2CSK4, and responses to CpG ODN appeared to be weak or absent (Fig.…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic profiling of bovine blood dendritic cells and monocytes following TLR stimulation

et al. 2020

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Dendritic cells (DC) and monocytes are vital for the initiation of innate and adaptive immune responses. Recently, we identified bona fide DC subsets in blood of cattle, revealing subset‐ and species‐specific transcription of toll‐like receptors (TLR). In the present study, we analyzed phenotypic and transcriptional responses of bovine DC subsets and monocytes to in vitro stimulation with four to six different TLR ligands. Bovine DC subsets, especially plasmacytoid DC (pDC), showed a clear increase of CCR7, CD25, CD40, CD80, CD86, and MHC‐II expression both on mRNA and protein level. Flow cytometric detection of p38 MAPK phosphorylation 15 min after stimulation confirmed activation of DC subsets and monocytes in accordance with TLR gene expression. Whole‐transcriptome sequencing of sorted and TLR‐stimulated subsets revealed potential ligand‐ and subset‐specific regulation of genes associated with inflammation, T‐cell co‐stimulation, migration, metabolic reprogramming, and antiviral activity. Gardiquimod was found to evoke strong responses both in DC subsets and monocytes, while Poly(I:C) and CpG preferentially triggered responses in cDC1 and pDC, respectively. This in‐depth analysis of ligand responsiveness is essential for the rational design of vaccine adjuvants in cattle, and provides a solid basis for comparative studies on DC and monocyte biology across species.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic profiling of bovine blood dendritic cells and monocytes following TLR stimulation

et al. 2020

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“…We chose to measure the expression of accessory molecules and 2 additional cytokines known to be produced by DCs and with an effect on biasing of T H differentiation: the proinflammatory cytokine IL-6 46 and the immunosuppressive cytokine IL-10. 5 Although IL-6 production is not affected by interference with FPR3 activation (see Fig E9, A-D), IL-10 is significantly upregulated ( Fig 6, A and B).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Peptides from allergenic lipocalins bind to formyl peptide receptor 3 in human dendritic cells to mediate TH2 immunity

Klaver

Posch

Geisler

et al. 2020

Journal of Allergy and Clinical Immunology

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Background: How T H 2-mediated allergic immune responses are induced is still under investigation. Objective: In an in vitro system we compared the effect of lipocalin allergens and nonallergenic homologues on human monocyte-derived dendritic cells (DCs) to investigate how they polarize naive CD4 1 T H cells. Microarray data gained with these DCs showed a significant difference in expression of formyl peptide receptors (FPRs). Activation of FPR3 in human monocyte-derived DCs leads to inhibition of IL-12 production. Low concentrations of IL-12 during T-cell priming biases immune responses toward T H 2. We hypothesize that binding of allergenic lipocalins to FPR3 might be a mechanism for induction of allergic immune responses. Methods: We examined whether lipocalins and FPR3 colocalize within the cells by using confocal microscopy. With calcium mobilization assays of FPR3-transfected HEK 293 cells, we measured FPR3 signaling in response to allergenic and nonallergenic lipocalins. Silencing of FPR3 in DCs and pretreatment with an antagonistic peptide were used to assess the function of FPR3 in T H 2 induction. Results: FPR3 and lipocalins colocalize in the same vesicles in DCs. Cathepsin S-digested allergenic lipocalins, but not digestion products of nonallergenic homologues, activate FPR3 signaling. FPR3 silencing in DCs or pretreatment with an antagonistic peptide restores IL-12 and induces IL-10 expression by DCs treated with lipocalin allergens, attenuating the T H 2 bias and inducing IL-10 production in cocultured T H cells. Conclusion: We describe a novel molecular mechanism for induction of T H 2-mediated allergic immune responses. (J

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“…CD40, a key molecule involved in DC activation and maturation, is deeply implicated in communication between DCs and T cells. This interaction relies on antigen presentation and subsequent helper and cytotoxic T-cell priming ( 86 , 87 ). Thus, any CD40 reprogramming of DCs will allow transplant tolerance, and with this in mind, Zang et al used a novel delivery method consisting of poly(ethylene glycol)- block -poly(lactide- co -glycolide) (PEG- b -PLGA)-based cationic lipid-assisted nanoparticles (CLANs).…”

Section: Advances In Genetic Engineering Of Immune Cellsmentioning

confidence: 99%

Using Gene Editing Approaches to Fine-Tune the Immune System

et al. 2020

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Genome editing technologies not only provide unprecedented opportunities to study basic cellular system functionality but also improve the outcomes of several clinical applications. In this review, we analyze various gene editing techniques used to finetune immune systems from a basic research and clinical perspective. We discuss recent advances in the development of programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-associated nucleases. We also discuss the use of programmable nucleases and their derivative reagents such as base editing tools to engineer immune cells via gene disruption, insertion, and rewriting of T cells and other immune components, such natural killers (NKs) and hematopoietic stem and progenitor cells (HSPCs). In addition, with regard to chimeric antigen receptors (CARs), we describe how different gene editing tools enable healthy donor cells to be used in CAR T therapy instead of autologous cells without risking graft-versus-host disease or rejection, leading to reduced adoptive cell therapy costs and instant treatment availability for patients. We pay particular attention to the delivery of therapeutic transgenes, such as CARs, to endogenous loci which prevents collateral damage and increases therapeutic effectiveness. Finally, we review creative innovations, including immune system repurposing, that facilitate safe and efficient genome surgery within the framework of clinical cancer immunotherapies.

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Immunomodulatory Bonds of the Partnership between Dendritic Cells and T Cells

Cited by 69 publications

References 241 publications

Transcriptomic profiling of bovine blood dendritic cells and monocytes following TLR stimulation

Transcriptomic profiling of bovine blood dendritic cells and monocytes following TLR stimulation

Peptides from allergenic lipocalins bind to formyl peptide receptor 3 in human dendritic cells to mediate TH2 immunity

Using Gene Editing Approaches to Fine-Tune the Immune System

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