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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

Ying Wang1, Zizhong Yu2, Yue Zhou1, Yun Zhu1, Jinhui Wang3, Junmei Fu4, Yang Yuan5, Shan Chen1, Yanjun Wang1, Wenting Yu1, Pei Gao1, Wanting Zhu1, Qing Cheng1, Seong H Cho6, Weijia Kong1, Jianjun Chen1
  • 1Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 2Department of Otorhinolaryngology, Taihe Hospital, Hubei University of Medicine, Wuhan, China
  • 3Department of Otorhinolaryngology, First Hospital of Handan, Wuhan, China
  • 4Department of Otorhinolaryngology, First People’s Hospital of Jiangxia District, Wuhan, China
  • 5Department of Otorhinolaryngology, Wuhan General Hospital of the Chinese People’s Liberation Army, Wuhan, China
  • 6Division of Allergy-Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
* Equal contribution
Received: June 26, 2020Accepted: September 9, 2020Published: November 24, 2020
https://doi.org/10.18632/aging.104145

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.