Research Paper Volume 12, Issue 24 pp 25432—25451
Different doses of ovalbumin exposure on dendritic cells determine their genetic/epigenetic regulation and T cell differentiation
- 1 Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2 Department of Otorhinolaryngology, Taihe Hospital, Hubei University of Medicine, Wuhan, China
- 3 Department of Otorhinolaryngology, First Hospital of Handan, Wuhan, China
- 4 Department of Otorhinolaryngology, First People’s Hospital of Jiangxia District, Wuhan, China
- 5 Department of Otorhinolaryngology, Wuhan General Hospital of the Chinese People’s Liberation Army, Wuhan, China
- 6 Division of Allergy-Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
Received: June 26, 2020 Accepted: September 9, 2020 Published: November 24, 2020
https://doi.org/10.18632/aging.104145How to Cite
Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
It has been reported that allergen dosage can impact the differentiation of dendritic cells (DCs)-mediated T cells. However, the mechanisms of such dose-dependent differentiation are poorly understood. In this study, bone marrow-derived immature DCs stimulated with Ovalbumin (OVA) of different concentrations (0, 10, 100, 1000, 10000μg/ml, respectively). DCs were then co-cultured with naïve T cells. RNA-sequencing detection and DNA methylation of DCs were performed. We show that when DCs were stimulated with low-dose (10μg/ml), 77 genes were up-regulated and 87 genes down-regulated. Most activated genes were related to ribosome synthesis and ion channel inhibition. At the medium-dose (100μg/ml), 339 genes were up-regulated and 168 genes down-regulated. Most activated genes involved cytokine synthesis and regulation of immune responses. At high-dose (10000μg/ml), 2497 genes were up-regulated and 1156 genes down-regulated. TNF signaling pathway, NF-kappa B signaling pathway, antigen processing and presentation signaling pathway were mostly up-regulated. The related co-stimulators, co-inhibitory molecules, inhibitory cytokines, negative regulating enzymes were highly expressed. The monocarbate, coenzyme, fatty acid, glucolipid, starch, sucrose and other metabolism-related signaling pathways were down-regulated. The profiles of DNA methylation and RNA synthesis of DCs varied with different doses of OVA, which serves to induce T cells to differentiate in various directions.
Abbreviations
DCs: Dendritic cells; Th cells: Helper T cells; Treg cells: Regulatory cells; Ovalbumin: OVA; RNA-seq: RNA sequencing technology; MACS: magnetic-activated cell sorting; DMRs: Differentially methylated regions; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; RPKM: Reads per Kilobase per Million Reads.