AUTHOR=Li He , Gao Yuehan , Xie Lihui , Wang Rong , Duan Runping , Li Zhaohuai , Chen Binyao , Zhu Lei , Wang Xianggui , Su Wenru TITLE=Prednisone Reprograms the Transcriptional Immune Cell Landscape in CNS Autoimmune Disease JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.739605 DOI=10.3389/fimmu.2021.739605 ISSN=1664-3224 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.