Identification of Small Molecule Inhibitors of a Mir155 Transcriptional Reporter in Th17 Cells
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 ave...
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Nature Portfolio
2021
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oai:doaj.org-article:28cf79f1b82146509af8f9f2b25584472021-12-02T15:57:20ZIdentification of Small Molecule Inhibitors of a Mir155 Transcriptional Reporter in Th17 Cells10.1038/s41598-021-90944-72045-2322https://doaj.org/article/28cf79f1b82146509af8f9f2b25584472021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90944-7https://doaj.org/toc/2045-2322Abstract 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.Anju SinghMyagmarjav DashynamBryan ChimThelma M. EscobarXiuhuai LiuXin HuSamarjit PatnaikXin XuNoel SouthallJuan MaruganAjit JadhavVanja LazarevicStefan A. MuljoMarc FerrerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Anju Singh Myagmarjav Dashynam Bryan Chim Thelma M. Escobar Xiuhuai Liu Xin Hu Samarjit Patnaik Xin Xu Noel Southall Juan Marugan Ajit Jadhav Vanja Lazarevic Stefan A. Muljo Marc Ferrer Identification of Small Molecule Inhibitors of a Mir155 Transcriptional Reporter in Th17 Cells |
| description |
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. |
| format |
article |
| author |
Anju Singh Myagmarjav Dashynam Bryan Chim Thelma M. Escobar Xiuhuai Liu Xin Hu Samarjit Patnaik Xin Xu Noel Southall Juan Marugan Ajit Jadhav Vanja Lazarevic Stefan A. Muljo Marc Ferrer |
| author_facet |
Anju Singh Myagmarjav Dashynam Bryan Chim Thelma M. Escobar Xiuhuai Liu Xin Hu Samarjit Patnaik Xin Xu Noel Southall Juan Marugan Ajit Jadhav Vanja Lazarevic Stefan A. Muljo Marc Ferrer |
| author_sort |
Anju Singh |
| title |
Identification of Small Molecule Inhibitors of a Mir155 Transcriptional Reporter in Th17 Cells |
| title_short |
Identification of Small Molecule Inhibitors of a Mir155 Transcriptional Reporter in Th17 Cells |
| title_full |
Identification of Small Molecule Inhibitors of a Mir155 Transcriptional Reporter in Th17 Cells |
| title_fullStr |
Identification of Small Molecule Inhibitors of a Mir155 Transcriptional Reporter in Th17 Cells |
| title_full_unstemmed |
Identification of Small Molecule Inhibitors of a Mir155 Transcriptional Reporter in Th17 Cells |
| title_sort |
identification of small molecule inhibitors of a mir155 transcriptional reporter in th17 cells |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/28cf79f1b82146509af8f9f2b2558447 |
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| _version_ |
1718385319746732032 |