Abstract

MicroRNA miR-155 is an important regulatory molecule in the immune system and is highly expressed and functional in Th17 cells, a subset of CD4+ T helper cells which are key players in autoimmune diseases. Small molecules that can modulate miR-155 may potentially provide new therapeutic avenues to inhibit Th17 cell-mediated autoimmune diseases. Here, we present a novel high-throughput screening assay using primary T cells from genetically engineered Mir155 reporter mice, and its use to screen libraries of small molecules to identify novel modulators of Th17 cell function. We have discovered a chemical series of (E)-1-(phenylsulfonyl)-2-styryl-1H-benzo[d] imidazoles as novel down-regulators of Mir155 reporter and cytokine expression in Th17 cells. In addition, we found that FDA approved antiparasitic agents belonging to the ‘azole’ family also down-regulate Mir155 reporter and cytokine expression in Th17 cells, and thus could potentially be repurposed to treat Th17-driven immunopathologies.

Details

Title
Identification of Small Molecule Inhibitors of a Mir155 Transcriptional Reporter in Th17 Cells
Author
Singh, Anju 1 ; Dashynam, Myagmarjav 1 ; Chim, Bryan 2 ; Escobar, Thelma M. 2 ; Liu, Xiuhuai 2 ; Hu, Xin 1 ; Patnaik, Samarjit 1 ; Xu, Xin 1 ; Southall, Noel 1 ; Marugan, Juan 1 ; Jadhav, Ajit 1 ; Lazarevic, Vanja 3 ; Muljo, Stefan A. 2 ; Ferrer, Marc 1 

 National Center for Advancing Translational Sciences (NCATS), NIH, Division of Preclinical Innovation, Rockville, USA (GRID:grid.429651.d) (ISNI:0000 0004 3497 6087) 
 National Institute of Allergy and Infectious Diseases, NIH, Laboratory of Immune System Biology, Bethesda, USA (GRID:grid.419681.3) (ISNI:0000 0001 2164 9667) 
 National Cancer Institute, National Institutes of Health, Experimental Immunology Branch, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2535620815
Copyright
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.