Prednisone Reprograms the Transcriptional Immune Cell Landscape in CNS Autoimmune Disease.

Abstract

Glucocorticoids (GCs) are widely used immunosuppressive drugs for autoimmune diseases, although considerable gaps exist between current knowledge of the mechanisms of GCs and their conclusive immune-regulatory effects. Here we generated a single-cell transcriptional immune cell atlas based on prednisone-treated or untreated experimental autoimmune uveitis (EAU) mice. Immune cells were globally activated in EAU, and prednisone partially reversed this effect in terms of cell composition, gene expression, transcription factor regulation, and cell-cell communication. Prednisone exerted considerable rescue effects on T and B cells and increased the proportion of neutrophils. Besides commonly regulated transcriptional factors (Fosb, Jun, Jund), several genes were only regulated in certain cell types (e.g. Cxcr4 and Bhlhe40 in T cells), suggesting cell-type-dependent immunosuppressive properties of GC. These findings provide new insights into the mechanisms behind the properties and cell-specific effects of GCs and can potentially benefit immunoregulatory therapy development.

• Authors: He Li, Yuehan Gao, Lihui Xie, Rong Wang, Runping Duan, Zhaohuai Li, Binyao Chen, Lei Zhu, Xianggui Wang, Wenru Su
• Journal: Frontiers in immunology (Front Immunol) Vol. 12 Pg. 739605 ( 2021) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 34484247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Li, Gao, Xie, Wang, Duan, Li, Chen, Zhu, Wang and Su.

Chemical References

• Glucocorticoids
• Prednisone

Topics

• Animals
• Autoimmune Diseases (drug therapy, genetics, immunology, metabolism)
• B-Lymphocytes (drug effects, immunology, metabolism)
• Disease Models, Animal
• Gene Expression Profiling
• Gene Regulatory Networks
• Glucocorticoids (pharmacology)
• Lymph Nodes (drug effects, immunology, metabolism)
• Mice
• Neutrophils (drug effects, enzymology, metabolism)
• Prednisone (pharmacology)
• RNA-Seq
• Single-Cell Analysis
• T-Lymphocytes (drug effects, immunology, metabolism)
• Transcriptome
• Uveitis (drug therapy, genetics, immunology, metabolism)