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Whole Transcriptome Analysis of Myeloid Dendritic Cells Reveals Distinct Genetic Regulation in Patients with Allergies.

ABSTRACT: Dendritic cells (DCs) play critical roles in atopic diseases, orchestrating both innate and adaptive immune systems. Nevertheless, limited information is available regarding the mechanism through which DCs induce hyperresponsiveness in patients with allergies. This study aims to reveal novel genetic alterations and future therapeutic target molecules in the DCs from patients with allergies using whole transcriptome sequencing. Transcriptome sequencing of human BDCA-3+/CD11c+ DCs sorted from peripheral blood monocytes obtained from six patients with allergies and four healthy controls was conducted. Gene expression profile data were analyzed, and an ingenuity pathway analysis was performed. A total of 1638 differentially expressed genes were identified at p-values < 0.05, with 11 genes showing a log2-fold change ?1.5. The top gene network was associated with cell death/survival and organismal injury/abnormality. In validation experiments, amphiregulin (AREG) showed consistent results with transcriptome sequencing data, with increased mRNA expression in THP-1-derived DCs after Der p 1 stimulation and higher protein expression in myeloid DCs obtained from patients with allergies. This study suggests an alteration in the expression of DCs in patients with allergies, proposing related altered functions and intracellular mechanisms. Notably, AREG might play a crucial role in DCs by inducing the Th2 immune response.

SUBMITTER: Lee K

PROVIDER: S-EPMC7697962 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Whole Transcriptome Analysis of Myeloid Dendritic Cells Reveals Distinct Genetic Regulation in Patients with Allergies.

Lee Kijeong K Han Mi-Ryung MR Yeon Ji Woo JW Kim Byoungjae B Kim Tae Hoon TH

International journal of molecular sciences 20201116 22

Dendritic cells (DCs) play critical roles in atopic diseases, orchestrating both innate and adaptive immune systems. Nevertheless, limited information is available regarding the mechanism through which DCs induce hyperresponsiveness in patients with allergies. This study aims to reveal novel genetic alterations and future therapeutic target molecules in the DCs from patients with allergies using whole transcriptome sequencing. Transcriptome sequencing of human BDCA-3+/CD11c+ DCs sorted from peri ...[more]

PMID: 33207814

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Project description:BackgroundPeripheral blood monocytes (PBMo) originate from the bone marrow, circulate in the blood and emigrate into various organs where they differentiate into tissue resident cellular phenotypes of the mononuclear phagocyte system, including macrophages (Mphi) and dendritic cells (DC). Like in other organs, this emigration and differentiation process is essential to replenish the mononuclear phagocyte pool in the lung under both inflammatory and non-inflammatory steady-state conditions. While many studies have addressed inflammation-driven monocyte trafficking to the lung, the emigration and pulmonary differentiation of PBMo under non-inflammatory conditions is much less understood.MethodsIn order to assess the transcriptional profile of circulating and lung resident mononuclear phagocyte phenotypes, PBMo, lung Mphi and lung DC from naïve mice were flow-sorted to high purity, and their gene expression was compared by DNA microarrays on a genome-wide scale. Differential regulation of selected genes was validated by quantitative PCR and on protein level by flow cytometry.ResultsDifferentially-expressed genes related to cell traffic were selected and grouped into the clusters (i) matrix metallopeptidases, (ii) chemokines/chemokine receptors, and (iii) integrins. Expression profiles of clustered genes were further assessed at the mRNA and protein levels in subsets of circulating PBMo (GR1- vs GR1+) and lung resident macrophages (alveolar vs interstitial Mphi). Our data identify differentially activated genetic programs in circulating monocytes and their lung descendents. Lung DC activate an extremely diverse set of gene families but largely preserve a mobile cell profile with high expression levels of integrin and chemokine/chemokine receptors. In contrast, interstitial and even more pronounced alveolar Mphi, stepwise downregulate gene expression of these traffic relevant communication molecules, but strongly upregulate a distinct set of matrix metallopetidases potentially involved in tissue invasion and remodeling.ConclusionOur data provide new insight in the changes of the genetic profiles of PBMo and their lung descendents, namely DC and Mphi under non-inflammatory, steady-state conditions. These findings will help to better understand the complex relations within the mononuclear phagocyte pool of the lung.

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Whole Transcriptome Analysis of Myeloid Dendritic Cells Reveals Distinct Genetic Regulation in Patients with Allergies.

Publications

Whole Transcriptome Analysis of Myeloid Dendritic Cells Reveals Distinct Genetic Regulation in Patients with Allergies.

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