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Updated: Nov 3, 2025
Small RNA Transfection in Primary Human Th17 Cells by Next Generation Electroporation
Published on: April 13, 2017
Identification of Small Molecule Inhibitors of a Mir155 Transcriptional Reporter in Th17 Cells
Anju Singh1, Myagmarjav Dashynam2, Bryan Chim3
1Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), NIH, 9800 Medical Center Drive, Rockville, MD, 20850, USA. anju.singh@nih.gov.
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.
Insights
Researchers identified novel small molecules that down-regulate microRNA miR-155 in T helper 17 (Th17) cells, offering potential treatments for autoimmune diseases.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- MicroRNA miR-155 is crucial in immune regulation and highly expressed in Th17 cells, which drive autoimmune diseases.
- Modulating miR-155 presents a therapeutic strategy for Th17 cell-mediated autoimmune conditions.
Purpose of the Study:
- To develop a high-throughput screening assay for identifying miR-155 modulators.
- To discover novel small molecules that inhibit Th17 cell function by targeting miR-155.
Main Methods:
- Utilized a high-throughput screening assay with primary T cells from genetically engineered Mir155 reporter mice.
- Screened chemical libraries to identify compounds affecting miR-155 reporter and cytokine expression in Th17 cells.
Main Results:
- Discovered a novel chemical series, (E)-1-(phenylsulfonyl)-2-styryl-1H-benzo[d]imidazoles, that down-regulates miR-155 and cytokine expression in Th17 cells.
- Identified FDA-approved 'azole' family antiparasitic agents as miR-155 down-regulators in Th17 cells.
Conclusions:
- Novel small molecules, including benzimidazole derivatives and azole antiparasitics, effectively down-regulate miR-155 in Th17 cells.
- These findings suggest potential therapeutic repurposing of existing drugs and development of new agents for autoimmune diseases.
