Transcriptomic Analysis Identifies A Tolerogenic Dendritic Cell Signature

Dendritic cells (DC) are central to regulating innate and adaptive immune responses. Strategies that modify DC function provide new therapeutic opportunities in autoimmune diseases and transplantation. Current pharmacological approaches can alter DC phenotype to induce tolerogenic DC (tolDC), a matu...

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Bibliographic Details
Published in:Frontiers in immunology 2021-10, Vol.12, p.733231-733231
Main Authors: Robertson, Harry, Li, Jennifer, Kim, Hani Jieun, Rhodes, Jake W, Harman, Andrew N, Patrick, Ellis, Rogers, Natasha M
Format: Article
Language:English
Subjects:
Databases, Genetic
dendritic cell
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - metabolism
gene expression profile analysis
Gene Expression Profiling
Humans
Immune Tolerance - genetics
Immunology
Lipopolysaccharides - pharmacology
mature dendritic cells
mononuclear phagocyte cells
Phenotype
Predictive Value of Tests
Reproducibility of Results
tolerogenic dendritic cell (tolDC)
Transcriptome
transcriptomic
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Summary:Dendritic cells (DC) are central to regulating innate and adaptive immune responses. Strategies that modify DC function provide new therapeutic opportunities in autoimmune diseases and transplantation. Current pharmacological approaches can alter DC phenotype to induce tolerogenic DC (tolDC), a maturation-resistant DC subset capable of directing a regulatory immune response that are being explored in current clinical trials. The classical phenotypic characterization of tolDC is limited to cell-surface marker expression and anti-inflammatory cytokine production, although these are not specific. TolDC may be better defined using gene signatures, but there is no consensus definition regarding genotypic markers. We address this shortcoming by analyzing available transcriptomic data to yield an independent set of differentially expressed genes that characterize human tolDC. We validate this transcriptomic signature and also explore gene differences according to the method of tolDC generation. As well as establishing a novel characterization of tolDC, we interrogated its translational utility , demonstrating this geneset was enriched in the liver, a known tolerogenic organ. Our gene signature will potentially provide greater understanding regarding transcriptional regulators of tolerance and allow researchers to standardize identification of tolDC used for cellular therapy in clinical trials.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.733231