Tolerogenic Transcriptional Signatures of Steady-State and Pathogen-Induced Dendritic Cells

Vendelova, Emilia; Ashour, DiyaaElDin; Blank, Patrick; Erhard, Florian; Kalinke, Ulrich; Lutz, Manfred B.

doi:10.3389/fimmu.2018.00333

Cited by 20 publications

(19 citation statements)

References 152 publications

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“…One of the first indications of potential pathways operating in professional antigen presenting cells [for the subtypes of DCs, the reader is referred to other reviews (68, 69)], was curiously obtained in a melanoma cell line. Grommé et al fractionated MelJuSo melanoma cells and identified HLA class I molecules in a fraction also containing acidic HLA class II loading compartments.…”

Section: Mhc Class I Recycling and Antigen Presentationmentioning

confidence: 99%

Endocytic Recycling of MHC Class I Molecules in Non-professional Antigen Presenting and Dendritic Cells

Montealegre

Endert

2019

Front. Immunol.

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Major histocompatibility complex class I (MHC I) molecules are glycoproteins that display peptide epitopes at the cell surface of nucleated cells for recognition by CD8+ T cells. Like other cell surface receptors, MHC class I molecules are continuously removed from the surface followed by intracellular degradation or recycling to the cell surface, in a process likely involving active quality control the mechanism of which remains unknown. The molecular players and pathways involved in internalization and recycling have previously been studied in model cell lines such as HeLa. However, dendritic cells (DCs), which rely on a specialized endocytic machinery that confers them the unique ability to “cross”-present antigens acquired by internalization, may use distinct MHC I recycling pathways and quality control mechanisms. By providing MHC I molecules cross-presenting antigens, these pathways may play an important role in one of the key functions of DCs, priming of T cell responses against pathogens and tumors. In this review, we will focus on endocytic recycling of MHC I molecules in various experimental conditions and cell types. We discuss the organization of the recycling pathway in model cell lines compared to DCs, highlighting the differences in the recycling rates and pathways of MHC I molecules between various cell types, and their putative functional consequences. Reviewing the literature, we find that conclusive evidence for significant recycling of MHC I molecules in primary DCs has yet to be demonstrated. We conclude that endocytic trafficking of MHC class I in DCs remains poorly understood and should be further studied because of its likely role in antigen cross-presentation.

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Section: Mhc Class I Recycling and Antigen Presentationmentioning

confidence: 99%

Endocytic Recycling of MHC Class I Molecules in Non-professional Antigen Presenting and Dendritic Cells

Montealegre

Endert

2019

Front. Immunol.

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“…Greenberg, 2014). Immature DCs inherently express T-cell co-stimulatory molecules only weakly; thus, they are prone to inducing anergic T cells (Pletinckx et al, 2015;Vendelova et al, 2018). However, our data indicate that weak costimulation of T cells by iDCs alone is not sufficient to mediate T-cell hyporeactivity, because production of extracellular Ado by CD73 was mandatory.…”

Section: Discussionmentioning

confidence: 81%

Production of Extracellular Adenosine by CD73+ Dendritic Cells Is Crucial for Induction of Tolerance in Contact Hypersensitivity Reactions

Silva-Vilches

Ring

Schrader

et al. 2019

Journal of Investigative Dermatology

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Dendritic cells (DCs) express the ecto-5 0-nucleotidase CD73 that generates immunosuppressive adenosine (Ado) by dephosphorylation of extracellular Ado monophosphate and diphosphate. To investigate whether CD73derived Ado has immune-suppressive activity, 2,4-dinitrothiocyanobenzene (DNTB) was applied to skin of wild-type (WT) or CD73-deficient (CD73 e/e) mice, followed by sensitization and challenge with 2,4dinitrofluorobenzene. In this model, we show the induction of tolerance by DNTB against 2,4dinitrofluorobenzene only in WT but not in CD73 e/e mice. Analysis of skin DCs showed increased expression of CD73 after application of DNTB in WT mice. That was accompanied by elevated concentrations of extracellular Ado in the lymph node. Moreover, T cells expressed markers for anergy, namely EGR2 and NDRG1 in DNTBtreated WT mice and they exhibited impaired proliferation upon ex vivo re-stimulation. Similarly, in vitro we observed that Ado-producing WT DCs, but not CD73 e/e DCs, rendered transgenic T cells from OTII mice (OTII T cells) hyporeactive, decreased their T-cell costimulatory signaling, and induced up-regulation of EGR2 and NDRG1. Thus, these data show that expression of CD73 by DCs, which triggers elevated levels of extracellular Ado, is a crucial mechanism for the induction of anergic T cells and tolerance.

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“…We then subdivided each DC subset into CD86 low MHC class II low -immature DCs and CD86 high MHC class II high -mature DCs ( Figure 2A) (15). The frequency of mature DCs among CD11c +total DCs increased at days 0.5 and 1.5 pc compared to that in virgin mice, and then returned to the level observed in virgin mice on days 2.5 and 3.5 pc ( Figures 2B,D,E).…”

Section: Mature Dcs Increase After Coitus and Decrease To Non-pregnanmentioning

confidence: 93%

“…For instance, IDO-expressing DCs and plasmacytoid DCs (pDCs) act as tolerogenic DCs (tDCs) (4). These tDCs have been shown to possess the capability of immunoregulation by inducing Tregs, as well as T cell, anergy and deletion (6,14,15). However, few reports have examined the characteristics of uDC subsets in murine pregnancy (2,4,(16)(17)(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Changes in the Phenotype of Dendritic Cells in the Uterus and Uterine Draining Lymph Nodes After Coitus

et al. 2020

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Dendritic cells (DCs) are essential for successful embryo implantation. However, the properties of uterine DCs (uDCs) during the implantation period are not well characterized. In this study, we investigated the dynamic changes in the uDC phenotypes during the period between coitus and implantation. In virgin mice, we evaluated the expressions of CD103 and XCR1, this is the first report to demonstrate uDCs expressing CD103 in XCR1 + cDC1s and XCR1 + cDC2s. On day 0.5 post coitus (pc), the number of uterine CD11c + CD103 − MHC classII high CD86 high-mature DCs rapidly increased and then decreased to non-pregnancy levels on days 1.5 and 2.5 pc. On day 3.5 pc just before implantation, the number of CD11c + CD103 + MHC class II dim CD86 dim-immature DCs increased in the uterus. The increase in mature uDCs on day 1.5 pc was observed in both allogeneic-and syngeneic mating, suggesting that sexual intercourse, or semen, play a role in this process. Meanwhile, the increase in immature uDCs on day 3.5 pc was only observed in allogeneic mating, suggesting that allo-antigens in the semen contribute to this process. Next, to understand the turnover and migration of uDCs, we monitored DC movement in the uterus and uterine draining lymph nodes (dLNs) using photoconvertible protein Kikume Green Red (KikGR) mice. On day 0.5 pc, uDCs were composed of equal numbers of remaining DCs and migratory DCs. However, on day 3.5 pc, uDCs were primarily composed of migratory DCs, suggesting that most of the uDCs migrate from the periphery just before implantation. Finally, we studied the expression of PD-L2-which induces immunoregulation-on DCs. On day 3.5 pc, PD-L2 was expressed on CD103 +-mature and CD103 −-mature DCs in the uterus. However, PD-L2 expression on CD103 −immature DCs and CD103 +-immature DCs was very low. Furthermore, both remaining and migratory DCs in the uterus and uterus-derived-DCs in the dLNs on day 3.5 pc highly expressed PD-L2 on their surface. Therefore, our study findings provide a better understanding of the dynamic changes occurring in uterine DCs and dLNs in preparation for implantation following allogeneic-and syngeneic mating.

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Tolerogenic Transcriptional Signatures of Steady-State and Pathogen-Induced Dendritic Cells

Cited by 20 publications

References 152 publications

Endocytic Recycling of MHC Class I Molecules in Non-professional Antigen Presenting and Dendritic Cells

Endocytic Recycling of MHC Class I Molecules in Non-professional Antigen Presenting and Dendritic Cells

Production of Extracellular Adenosine by CD73+ Dendritic Cells Is Crucial for Induction of Tolerance in Contact Hypersensitivity Reactions

Dynamic Changes in the Phenotype of Dendritic Cells in the Uterus and Uterine Draining Lymph Nodes After Coitus

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