Different doses of ovalbumin exposure on dendritic cells determine their genetic/epigenetic regulation and T cell differentiation

• Published in: Aging (Albany, NY.) NY.), 2020-12, Vol.12 (24), p.25432-25451
• Main Authors: Wang, Ying, Yu, Zizhong, Zhou, Yue, Zhu, Yun, Wang, Jinhui, Fu, Junmei, Yuan, Yang, Chen, Shan, Wang, Yanjun, Yu, Wenting, Gao, Pei, Zhu, Wanting, Cheng, Qing, Cho, Seong H, Kong, Weijia, Chen, Jianjun
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - drug effects; Coculture Techniques; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - metabolism; DNA Methylation - drug effects; Dose-Response Relationship, Drug; Epigenesis, Genetic - drug effects; Female; Gene Expression Regulation - drug effects; Mice; Mice, Inbred BALB C; Ovalbumin - administration & dosage; Research Paper; Signal Transduction - drug effects; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.104145

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.