Mice Plasmacytoid Dendritic Cells Were Activated by Lipopolysaccharides Through Toll-Like Receptor 4/Myeloid Differentiation Factor 2

Zhang, Wei; An, Eun‐Koung; Hwang, Juyoung; Jin, Jun‐O

doi:10.3389/fimmu.2021.727161

Cited by 7 publications

(6 citation statements)

References 48 publications

(59 reference statements)

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“…The abundance of DCs was significantly positively correlated with the abundance of T cells and cytotoxic lymphocytes in tumor tissues ( Supplementary Figures S5A, B ), partly validating the findings of the scRNA sequencing data analysis. The subpopulation of cells with high expression of BIRC3 was involved in tumor suppressive regulatory role ( Andersen et al, 2017 ; Nakamizo et al, 2021 ), while IRF7 recruited activated inflammatory cells producing interferons ( Tomasello et al, 2018 ; Zhang et al, 2021d ; Somebang et al, 2021 ). Paradoxically, MAT2A and SOX4 were highly expressed in this cluster.…”

Section: Resultsmentioning

confidence: 99%

Mapping the tumor microenvironment in clear cell renal carcinoma by single-cell transcriptome analysis

Wang

Liu

et al. 2023

Front. Genet.

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Introduction: Clear cell renal cell carcinoma (ccRCC) is associated with unfavorable clinical outcomes. To identify viable therapeutic targets, a comprehensive understanding of intratumoral heterogeneity is crucial. In this study, we conducted bioinformatic analysis to scrutinize single-cell RNA sequencing data of ccRCC tumor and para-tumor samples, aiming to elucidate the intratumoral heterogeneity in the ccRCC tumor microenvironment (TME).Methods: A total of 51,780 single cells from seven ccRCC tumors and five para-tumor samples were identified and grouped into 11 cell lineages using bioinformatic analysis. These lineages included tumor cells, myeloid cells, T-cells, fibroblasts, and endothelial cells, indicating a high degree of heterogeneity in the TME. Copy number variation (CNV) analysis was performed to compare CNV frequencies between tumor and normal cells. The myeloid cell population was further re-clustered into three major subgroups: monocytes, macrophages, and dendritic cells. Differential expression analysis, gene ontology, and gene set enrichment analysis were employed to assess inter-cluster and intra-cluster functional heterogeneity within the ccRCC TME.Results: Our findings revealed that immune cells in the TME predominantly adopted an inflammatory suppression state, promoting tumor cell growth and immune evasion. Additionally, tumor cells exhibited higher CNV frequencies compared to normal cells. The myeloid cell subgroups demonstrated distinct functional properties, with monocytes, macrophages, and dendritic cells displaying diverse roles in the TME. Certain immune cells exhibited pro-tumor and immunosuppressive effects, while others demonstrated antitumor and immunostimulatory properties.Conclusion: This study contributes to the understanding of intratumoral heterogeneity in the ccRCC TME and provides potential therapeutic targets for ccRCC treatment. The findings emphasize the importance of considering the diverse functional roles of immune cells in the TME for effective therapeutic interventions.

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Section: Resultsmentioning

confidence: 99%

Mapping the tumor microenvironment in clear cell renal carcinoma by single-cell transcriptome analysis

Wang

Liu

et al. 2023

Front. Genet.

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“…LPS (TLR4 ligand) and bacterial CpG-DNA (TLR9 agonist) are capable of inducing a functional interaction of NF-κB with the promoter element of HLA-DRA to induce MHC-II gene expression and of increasing CD86 expression in both a TLR4-dependent or TLR9-dependent manner. 37 – 39 Interestingly, neutralization of diS-HMGB1 increased expression of the immune checkpoint PD-L1 but TLR inhibition decreased its expression. TLR9 is reported to induce PD-L1 in dendritic cells (DCs), suggesting that TLR2, CXCR4, or another HMGB1 receptor not examined in this study competitively regulates myeloid PD-L1 to ultimately decrease its expression.…”

Section: Discussionmentioning

confidence: 99%

Disulfide-HMGB1 signals through TLR4 and TLR9 to induce inflammatory macrophages capable of innate-adaptive crosstalk in human liver transplantation

Terry¹,

Kojima²,

Sosa³

et al. 2023

American Journal of Transplantation

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“…In our experiments, we found that the Gram-negative bacteria E. coli provides the strongest priming signal for human pDCs when compared to Gram-positive bacteria strains and the opportunistic fungi Candida albicans . However, similar to treatments with synthetic TLR ligands, E. coli alone did not induce mature IL-1β release, which is likely due to the fact that human pDCs, unlike mouse pDCs, do not express TLR4 [ 5 , 121 ].…”

Section: Discussionmentioning

confidence: 99%

Interactions between the NLRP3-Dependent IL-1β and the Type I Interferon Pathways in Human Plasmacytoid Dendritic Cells

Bencze

Fekete²,

Pfliegler³

et al. 2022

IJMS

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Generally, a reciprocal antagonistic interaction exists between the antiviral type I interferon (IFN) and the antibacterial nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3)-dependent IL-1β pathways that can significantly shape immune responses. Plasmacytoid dendritic cells (pDCs), as professional type I IFN-producing cells, are the major coordinators of antiviral immunity; however, their NLRP3-dependent IL-1β secretory pathway is poorly studied. Our aim was to determine the functional activity of the IL-1β pathway and its possible interaction with the type I IFN pathway in pDCs. We found that potent nuclear factor-kappa B (NF-κB) inducers promote higher levels of pro-IL-1β during priming compared to those activation signals, which mainly trigger interferon regulatory factor (IRF)-mediated type I IFN production. The generation of cleaved IL-1β requires certain secondary signals in pDCs and IFN-α or type I IFN-inducing viruses inhibit IL-1β production of pDCs, presumably by promoting the expression of various NLRP3 pathway inhibitors. In line with that, we detected significantly lower IL-1β production in pDCs of psoriasis patients with elevated IFN-α levels. Collectively, our results show that the NLRP3-dependent IL-1β secretory pathway is inducible in pDCs; however, it may only prevail under inflammatory conditions, in which the type I IFN pathway is not dominant.

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Mice Plasmacytoid Dendritic Cells Were Activated by Lipopolysaccharides Through Toll-Like Receptor 4/Myeloid Differentiation Factor 2

Cited by 7 publications

References 48 publications

Mapping the tumor microenvironment in clear cell renal carcinoma by single-cell transcriptome analysis

Mapping the tumor microenvironment in clear cell renal carcinoma by single-cell transcriptome analysis

Disulfide-HMGB1 signals through TLR4 and TLR9 to induce inflammatory macrophages capable of innate-adaptive crosstalk in human liver transplantation

Interactions between the NLRP3-Dependent IL-1β and the Type I Interferon Pathways in Human Plasmacytoid Dendritic Cells

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